Induced pluripotent stem cell

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cell in the body. This is particularly important because many other types of human cells derived from patients tend to stop growing after a few passages in laboratory culture. iPS cells have been generated for a wide variety of human genetic diseases, including common disorders such as Down syndrome and polycystic kidney disease. In many instances, the patient-derived iPS cells exhibit cellular defects not observed in iPS cells from healthy subjects, providing insight into the pathophysiology of the disease. An international collaborated project, StemBANCC, was formed in 2012 to build a collection of iPS cell lines for drug screening for a variety of diseases. Managed by the

574:(cancer-causing genes) may potentially be triggered. In February 2008, scientists announced the discovery of a technique that could remove oncogenes after the induction of pluripotency, thereby increasing the potential use of iPS cells in human diseases. In another study, Yamanaka reported that one can create iPSCs without the oncogene c-Myc. The process took longer and was not as efficient, but the resulting chimeras did not develop cancer. Inactivation or deletion of the tumor suppressor p53, which is a key regulator of cancer, significantly increases reprogramming efficiency. Thus there seems to be a tradeoff between reprogramming efficiency and tumor generation. 756: 1468: 700:). Although the plasmid methods avoid viruses, they still require cancer-promoting genes to accomplish reprogramming. The other main issue with these methods is that they tend to be much less efficient compared to retroviral methods. Furthermore, transfected plasmids have been shown to integrate into the host genome and therefore they still pose the risk of insertional mutagenesis. Because non-retroviral approaches have demonstrated such low efficiency levels, researchers have attempted to effectively rescue the technique with what is known as the 1039:

integration of transgenes face the problems of incomplete reprogramming and tumor genesis, although a vast number of techniques and methods have been attempted. Another large set of strategies is to perform a proteomic characterization of iPS cells. Further studies and new strategies should generate optimal solutions to the five main challenges. One approach might attempt to combine the positive attributes of these strategies into an ultimately effective technique for reprogramming cells to iPS cells.

6081: 601: 185: 56: 6461: 405:, fail to elicit induction, thus demonstrating the exclusiveness of Oct-3/4 to the induction process. Schöler showed that Oct4 overexpression during reprogramming causes epigenetic changes deteriorating the quality of iPSCs. Comparing to OSKM (Oct4, Sox2, Klf4 and c-Myc) new SKM (Sox2, Klf4 and c-Myc) reprogramming generates iPSCs with developmental potential equivalent to embryonic stem cell, as determined by their ability to generate all-iPSC mice through 1060:, the effort pooled funds and resources from 10 pharmaceutical companies and 23 universities. The goal is to generate a library of 1,500 iPS cell lines which will be used in early drug testing by providing a simulated human disease environment. Furthermore, combining hiPSC technology and small molecule or genetically encoded voltage and calcium indicators provided a large-scale and high-throughput platform for cardiovascular drug safety screening. 747:

mechanisms have been proposed. ES cell-specific microRNA molecules (such as miR-291, miR-294 and miR-295) enhance the efficiency of induced pluripotency by acting downstream of c-Myc. MicroRNAs can also block expression of repressors of Yamanaka's four transcription factors, and there may be additional mechanisms induce reprogramming even in the absence of added exogenous transcription factors.

944:: iPS cells from mouse fetal fibroblasts injected into tetraploid blastocysts (which themselves can only form extra-embryonic tissues) can form whole, non-chimeric, fertile mice, although with low success rate. The efficiency of all-PSC mouse production could boosted by a short exposure of pluripotent stem cell line to an episomal plasmid encoding for engineered Sox2 and Klf4 (SK cocktail). 628:(HDAC) inhibitor valproic acid. They found that it increased reprogramming efficiency 100-fold (compared to Yamanaka's traditional transcription factor method). The researchers proposed that this compound was mimicking the signaling that is usually caused by the transcription factor c-Myc. A similar type of compensation mechanism was proposed to mimic the effects of 648:(MET) process in which fibroblasts are pushed to a stem-cell like state, Ding's group identified two chemicals – ALK5 inhibitor SB431412 and MEK (mitogen-activated protein kinase) inhibitor PD0325901 – which was found to increase the efficiency of the classical genetic method by 100 fold. Adding a third compound known to be involved in the cell survival pathway, 284:, published studies that substantially improved on the reprogramming approach, giving rise to iPSCs that were indistinguishable from ESCs. Unlike the first generation of iPSCs, these second generation iPSCs produced viable chimeric mice and contributed to the mouse germline, thereby achieving the 'gold standard' for pluripotent stem cells. 684:

its own genes into the targeted host and avoids the potential for insertional mutagenesis. In 2009, Freed et al. demonstrated successful reprogramming of human fibroblasts to iPS cells. Another advantage of using adenoviruses is that they only need to present for a brief amount of time in order for effective reprogramming to take place.

1024:, which indicated that the cells were tolerated by the immune system. In 2013, Araki et al. attempted to reproduce the conclusion obtained by Zhou et al. using a different procedure. They took cells from a chimera that had been grown from IPSC clones and a mouse embryo, this tissue was then transplanted into 496:: In embryonic stem cells, Nanog, along with Oct-3/4 and Sox2, is necessary in promoting pluripotency. Therefore, it was surprising when Yamanaka et al. reported that Nanog was unnecessary for induction although Thomson et al. has reported it is possible to generate iPS cells with Nanog as one of the factors. 1195:

On March 9, 2018, the Specified Regenerative Medicine Committee of Osaka University officially approved the world's first clinical research plan to transplant a "myocardial sheet" made from iPS cells into the heart of patients with severe heart failure. Osaka University announced that it had filed an

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for a few days, the liver buds were transplanted into mice where the 'liver' quickly connected with the host blood vessels and continued to grow. Most importantly, it performed regular liver functions including metabolizing drugs and producing liver-specific proteins. Further studies will monitor the

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A more recent study on motor functional recovery after spinal cord injuries in mice showed that after human-induced pluripotent stem cells were transplanted into the mice, the cells differentiated into three neural lineages in the spinal cord. The cells stimulated regrowth of the damaged spinal cord,

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in the plasma membrane in order to increase reprogramming efficiency. Deng et al. of Beijing University reported in July 2013 that induced pluripotent stem cells can be created without any genetic modification. They used a cocktail of seven small-molecule compounds including DZNep to induce the mouse

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Upon delivery of all twenty-four factors, ESC-like colonies emerged that reactivated the Fbx15 reporter and could propagate indefinitely. To identify the genes necessary for reprogramming, the researchers removed one factor at a time from the pool of twenty-four. By this process, they identified four

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A non-genetic method of producing iPSCs has been demonstrated using recombinant proteins, but its efficiency was quite low. However, refinements to this methodology yielding higher efficiency may lead to production of safer iPSCs. Other approaches such as using adenoviruses or plasmids are generally

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Also in 2008, Yamanaka et al. found that they could transfer the four necessary genes with a plasmid. The Yamanaka group successfully reprogrammed mouse cells by transfection with two plasmid constructs carrying the reprogramming factors; the first plasmid expressed c-Myc, while the second expressed

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that can mimic the effects of transcription factors. These compounds can compensate for a reprogramming factor that does not effectively target the genome or fails at reprogramming for another reason; thus they raise reprogramming efficiency. They also avoid the problem of genomic integration, which

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Obtaining fibroblasts to produce iPSCs involves a skin biopsy, and there has been a push towards identifying cell types that are more easily accessible. In 2008, iPSCs were derived from human keratinocytes, which could be obtained from a single hair pluck. In 2010, iPSCs were derived from peripheral

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In June 2014, Takara Bio received technology transfer from iHeart Japan, a venture company from Kyoto University's iPS Cell Research Institute, to make it possible to exclusively use technologies and patents that induce differentiation of iPS cells into cardiomyocytes in Asia. The company announced

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mice. They conducted a similar trial using ES cells instead of IPSC clone and compared the results. Findings indicate that there was no significant difference in the immunogenic response produced by the IPS cells and the ES cells. Furthermore, Araki et al. reported little or no immunogenic response

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implicated in cancer. Yamanaka et al. and Jaenisch et al. demonstrated that c-myc is a factor implicated in the generation of mouse iPS cells and Yamanaka et al. demonstrated it was a factor implicated in the generation of human iPS cells. However, Thomson et al., Yamanaka et al. usage of the "myc"

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of the Klf family of transcription factors was initially identified by Yamanaka et al. and confirmed by Jaenisch et al. As a factor for the generation of mouse iPS cells and was demonstrated by Yamanaka et al. as a factor for generation of human iPS cells. However, Thomson et al. reported that Klf4

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cells could be used to generate transplants without the risk of immune rejection. While the iPSC technology has not yet advanced to a stage where therapeutic transplants have been deemed safe, iPSCs are readily being used in personalized drug discovery efforts and understanding the patient-specific

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Since iPSCs can only be produced with high efficiency at this time using modifications, they are generally predicted to be less safe and more tumorigenic than hESC. All the genes that have been shown to promote iPSC formation have also been linked to cancer in one way or another. Some of the genes

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were found to be extremely similar between ES and iPS cells. The generated iPSCs were remarkably similar to naturally isolated pluripotent stem cells (such as mouse and human embryonic stem cells, mESCs and hESCs, respectively) in the following respects, thus confirming the identity, authenticity,

704:. Several studies have demonstrated that this system can effectively deliver the key reprogramming factors without leaving footprint mutations in the host cell genome. The PiggyBac Transposon System involves the re-excision of exogenous genes, which eliminates the issue of insertional mutagenesis. 683:

In 2008, Hochedlinger et al. used an adenovirus to transport the requisite four transcription factors into the DNA of skin and liver cells of mice, resulting in cells identical to ESCs. The adenovirus is unique from other vectors like viruses and retroviruses because it does not incorporate any of

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An attractive feature of human iPS cells is the ability to derive them from adult patients to study the cellular basis of human disease. Since iPS cells are self-renewing and pluripotent, they represent a theoretically unlimited source of patient-derived cells which can be turned into any type of

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Genomic Insertion: genomic integration of the transcription factors limits the utility of the transcription factor approach because of the risk of mutations being inserted into the target cell's genome. A common strategy for avoiding genomic insertion has been to use a different vector for input.

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cells were reprogrammed into iPS cells in Yamanaka's original mouse study was 0.01–0.1%. The low efficiency rate may reflect the need for precise timing, balance, and absolute levels of expression of the reprogramming genes. It may also suggest a need for rare genetic or epigenetic changes in the

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Concern regarding the immunogenicity of IPS cells arose in 2011 when Zhou et al. performed a study involving a teratoma formation assay and demonstrated that IPS cells produced an immune response strong enough to cause rejection of the cells. When a similar procedure was performed on genetically

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An important area for future studies in the iPSC field is directly testing iPSC tumorigenicity using methods that mimic the approaches that would be used for regenerative medicine therapies. Such studies are crucial since iPSCs not only form teratoma, but also mice derived from iPSCs have a high

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by preventing the activity of expression proteins, or by recruiting enzymes that interfere with expression. Thus, methylation of a gene effectively silences it by preventing transcription. Promoters of pluripotency-associated genes, including Oct-3/4, Rex1, and Nanog, were demethylated in iPSCs,

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are short RNA molecules that bind to complementary sequences on messenger RNA and block expression of a gene. Measuring variations in microRNA expression in iPS cells can be used to predict their differentiation potential. Addition of microRNAs can also be used to enhance iPS potential. Several

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somatic cells into stem cells which they called CiPS cells with the efficiency – at 0.2% – comparable to those using standard iPSC production techniques. The CiPS cells were introduced into developing mouse embryos and were found to contribute to all major cells types, proving its pluripotency.

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maintained myelination, and formed synapses. These positive outcomes were observed for over 112 days after the spinal cord injury, without tumor formation. Nevertheless, a follow-up study by the same group showed distinct clones of human-induced pluripotent stem cells eventually formed tumors.

550:) complex. Overexpression of Mbd3, a subunit of NuRD, inhibits induction of iPSCs. Depletion of Mbd3, on the other hand, improves reprogramming efficiency, that results in deterministic and synchronized iPS cell reprogramming (near 100% efficiency within seven days from mouse and human cells). 1038:

The task of producing iPS cells continues to be challenging due to the six problems mentioned above. A key tradeoff to overcome is that between efficiency and genomic integration. Most methods that do not rely on the integration of transgenes are inefficient, while those that do rely on the

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completed the first successful transplant of iPS-derived retinal cells from a donor into the eye of a person with advanced macular degeneration. However it was reported that they are now having complications. The benefits of using autologous iPSCs are that there is theoretically no risk of

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iPSC derivation is typically a slow and inefficient process, taking one–two weeks for mouse cells and three–four weeks for human cells, with efficiencies around 0.01–0.1%. However, considerable advances have been made in improving the efficiency and the time it takes to obtain iPSCs. Upon

252:, Japan, in 2006. They hypothesized that genes important to embryonic stem cell (ESC) function might be able to induce an embryonic state in adult cells. They chose twenty-four genes previously identified as important in ESCs and used retroviruses to deliver these genes to mouse 836:

Stem cell markers: iPSCs expressed cell surface antigenic markers expressed on ESCs. Human iPSCs expressed the markers specific to hESC, including SSEA-3, SSEA-4, TRA-1-60, TRA-1-81, TRA-2-49/6E, and Nanog. Mouse iPSCs expressed SSEA-1 but not SSEA-3 nor SSEA-4, similarly to

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are compacting proteins that are structurally localized to DNA sequences that can affect their activity through various chromatin-related modifications. H3 histones associated with Oct-3/4, Sox2, and Nanog were demethylated, indicating the expression of Oct-3/4, Sox2, and

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In January 2014, two articles were published claiming that a type of pluripotent stem cell can be generated by subjecting the cells to certain types of stress (bacterial toxin, a low pH of 5.7, or physical squeezing); the resulting cells were called STAP cells, for

228:, small molecules, or even non-related genes such as lineage specifiers. It is also clear that pro-mitotic factors such as C-MYC/L-MYC or repression of cell cycle checkpoints, such as p53, are conduits to creating a compliant cellular state for iPSC reprogramming. 417:: The Sox family of transcription factors is associated with maintaining pluripotency similar to Oct-3/4, although it is associated with multipotent and unipotent stem cells in contrast with Oct-3/4, which is exclusively expressed in pluripotent stem cells. While 1255:. However the trial was suspended after Japan's new regenerative medicine laws came into effect in November 2015. More specifically, an existing set of guidelines was strengthened to have the force of law (previously mere recommendations). iPSCs derived from 128:. Because they can propagate indefinitely, as well as give rise to every other cell type in the body (such as neurons, heart, pancreatic, and liver cells), they represent a single source of cells that could be used to replace those lost to damage or disease. 207:

iPSCs are typically derived by introducing products of specific sets of pluripotency-associated genes, or "reprogramming factors", into a given cell type. The original set of reprogramming factors (also dubbed Yamanaka factors) are the transcription factors

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Thornton, Christopher D.; Fielding, Stuart; Karbowniczek, Kinga; Roig-Merino, Alicia; Burrows, Alysha E.; FitzPatrick, Lorna M.; Sharaireh, Aseel; Tite, John P.; Mole, Sara E.; Harbottle, Richard P.; Caproni, Lisa J.; McKay, Tristan R. (10 December 2021).

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Other considerations for starting cell type include mutational load (for example, skin cells may harbor more mutations due to UV exposure), time it takes to expand the population of starting cells, and the ability to differentiate into a given cell type.

972:, more than to any other cell type. However, on the order of a thousand sites show differences in several iPS cell lines. Half of these resemble the somatic cell line the iPS cells were derived from, the rest are iPSC-specific. Tens of regions which are 146:

Since iPSCs can be derived directly from adult tissues, they not only bypass the need for embryos, but can be made in a patient-matched manner, which means that each individual could have their own pluripotent stem cell line. These unlimited supplies of

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These second-generation iPSCs were derived from mouse fibroblasts by retroviral-mediated expression of the same four transcription factors (Oct4, Sox2, cMyc, Klf4). However, instead of using Fbx15 to select for pluripotent cells, the researchers used

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The table on the right summarizes the key strategies and techniques used to develop iPS cells in the first five years after Yamanaka et al.'s 2006 breakthrough. Rows of similar colors represent studies that used similar strategies for reprogramming.

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who was the first to derive human embryonic stem cells. With the same principle used in mouse reprogramming, Yamanaka's group successfully transformed human fibroblasts into iPSCs with the same four pivotal genes, Oct4, Sox2, Klf4, and cMyc, using a

826:. Colonies of iPSCs were also similar to that of ESCs. Human iPSCs formed sharp-edged, flat, tightly packed colonies similar to hESCs and mouse iPSCs formed the colonies similar to mESCs, less flat and more aggregated colonies than that of hESCs. 1286:

New clinical trials involving iPSCs are now ongoing not only in Japan, but also in the US and Europe. Research in 2021 on the trial registry Clinicaltrials.gov identified 129 trial listings mentioning iPSCs, but most were non-interventional.

930:) differentiates into extraembryonic tissues. The hollow trophoblast is unable to form a living embryo, and thus it is necessary for the embryonic stem cells within the embryoblast to differentiate and form the embryo. iPSCs were injected by 569:

Tumorigenicity: Depending on the methods used, reprogramming of adult cells to obtain iPSCs may pose significant risks that could limit their use in humans. For example, if viruses are used to genomically alter the cells, the expression of

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introduction of reprogramming factors, cells begin to form colonies that resemble pluripotent stem cells, which can be isolated based on their morphology, conditions that select for their growth, or through expression of surface markers or

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also generate iPSCs, although with decreased efficiency. Velychko et al. engineered a chimeric super-reprogramming factor, Sox2-17 or "super-Sox", which enhanced or allowed generation of mouse, human, cynomolgus monkey, porcine and bovine

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Another approach is the use of iPS cells derived from patients to identify therapeutic drugs able to rescue a phenotype. For instance, iPS cell lines derived from patients affected by ectodermal dysplasia syndrome (EEC), in which the

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MacCarthy, Caitlin M.; Wu, Guangming; Malik, Vikas; Menuchin-Lasowski, Yotam; Velychko, Taras; Keshet, Gal; Fan, Rui; Bedzhov, Ivan; Church, George M.; Jauch, Ralf; Cojocaru, Vlad; Schöler, Hans R.; Velychko, Sergiy (December 2023).

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Serrano, Ricardo; Feyen, Dries A.M.; Bruyneel, Arne A.N.; Hnatiuk, Anna P.; Vu, Michelle M.; Amatya, Prashila L.; Perea-Gil, Isaac; Prado, Maricela; Seeger, Timon; Wu, Joseph C.; Karakikes, Ioannis; Mercola, Mark (January 2023).

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This timeline summarizes the key strategies and techniques used to develop iPS cells in the first five years after Yamanaka et al.'s 2006 breakthrough. Rows of similar colors represent studies that used similar strategies for

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McKeithan, Wesley L.; Feyen, Dries A. M.; Bruyneel, Arne A. N.; Okolotowicz, Karl J.; Ryan, Daniel A.; Sampson, Kevin J.; Potet, Franck; Savchenko, Alex; Gómez-Galeno, Jorge; Vu, Michelle; Serrano, Ricardo (5 November 2020).

359:(Sox1, Sox2, Sox3, and Sox15) have been identified as crucial transcriptional regulators involved in the induction process whose absence makes induction impossible. Additional genes, however, including certain members of the 5840:"Information on p=roposed pilot study of the safety and feasibility of transplantation of autologous hiPSC-derived retinal pigment epithelium (RPE) cell sheets in patients with neovascular age-related macular degeneration" 915:", which consist of a core of mitotically active and differentiating hESCs and a periphery of fully differentiated cells from all three germ layers. iPSCs also form embryoid bodies and have peripheral differentiated cells. 5926: 1016:

incidence of death from malignant cancer. A 2010 paper was published in the journal Stem Cells indicating that iPS cells are far more tumorigenic than ESC, supporting the notion that iPS cell safety is a serious concern.

191:(1) Isolate and culture donor cells. (2) Transduce stem cell-associated genes into the cells by viral vectors. Red cells indicate the cells expressing the exogenous genes. (3) Harvest and culture the cells according to 1351:

A multipotent mesenchymal stem cell, when induced into pluripotence, holds great promise to slow or reverse aging phenotypes. Such anti-aging properties were demonstrated in early clinical trials in 2017. In 2020,

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In April 2009, it was demonstrated that generation of iPS cells is possible without any genetic alteration of the adult cell: a repeated treatment of the cells with certain proteins channeled into the cells via

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Feyen, Dries A. M.; McKeithan, Wesley L.; Bruyneel, Arne A. N.; Spiering, Sean; Hörmann, Larissa; Ulmer, Bärbel; Zhang, Hui; Briganti, Francesca; Schweizer, Michaela; Hegyi, Bence; Liao, Zhandi (21 July 2020).

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differentiation, and presence of Oct-3/4 thus gives rise to the pluripotency and differentiation potential of embryonic stem cells. Various other genes in the "Oct" family, including Oct-3/4's close relatives,

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In light of difficulties that other labs had replicating the results of the surprising study, in March 2014, one of the co-authors has called for the articles to be retracted. On 4 June 2014, the lead author,

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Araki R, Uda M, Hoki Y, Sunayama M, Nakamura M, Ando S, et al. (February 2013). "Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells".

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Sharma, Arun; Burridge, Paul W.; McKeithan, Wesley L.; Serrano, Ricardo; Shukla, Praveen; Sayed, Nazish; Churko, Jared M.; Kitani, Tomoya; Wu, Haodi; Holmström, Alexandra; Matsa, Elena (15 February 2017).

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Although a pint of donated blood contains about two trillion red blood cells and over 107 million blood donations are collected globally, there is still a critical need for blood for transfusion. In 2014,

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and then red blood cells. The final step was to make them eject their nuclei and mature properly. Type O can be transfused into all patients. Human clinical trials were not expected to begin before 2016.

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activity are cornerstones of ESCs, as stem cells must self-renew as part of their definition. iPSCs were mitotically active, actively self-renewing, proliferating, and dividing at a rate equal to ESCs.

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was the initial gene used for induction by Yamanaka et al., Jaenisch et al., and Thomson et al., other transcription factors in the Sox family have been found to work as well in the induction process.

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researchers concluded after studying elderly mice that old human cells when subjected to the Yamanaka factors, might rejuvenate and become nearly indistinguishable from their younger counterparts.

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Chen Y, Lüttmann FF, Schoger E, Schöler HR, Zelarayán LC, Kim KP, et al. (September 2021). "Reversible reprogramming of cardiomyocytes to a fetal state drives heart regeneration in mice".

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McKeithan, Wesley L.; Savchenko, Alex; Yu, Michael S.; Cerignoli, Fabio; Bruyneel, Arne A. N.; Price, Jeffery H.; Colas, Alexandre R.; Miller, Evan W.; Cashman, John R.; Mercola, Mark (2017).

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Maekawa M, Yamaguchi K, Nakamura T, Shibukawa R, Kodanaka I, Ichisaka T, et al. (June 2011). "Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1".

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Induced pluripotent stem cells are similar to natural pluripotent stem cells, such as embryonic stem cells, in many aspects, such as the expression of certain stem cell genes and proteins,

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further increases the efficiency by 200 fold. Using the combination of these three compounds also decreased the reprogramming process of the human fibroblasts from four weeks to two weeks.

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of ~50 cell divisions. hESCs express high telomerase activity to sustain self-renewal and proliferation, and human iPSCs also demonstrate high telomerase activity and express hTERT (human

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Aasen T, Raya A, Barrero MJ, Garreta E, Consiglio A, Gonzalez F, et al. (November 2008). "Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes".

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family of genes in induction of iPS cells is troubling for the eventuality of iPS cells as clinical therapies, as 25% of mice transplanted with c-myc-induced iPS cells developed lethal

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Although the methods pioneered by Yamanaka and others have demonstrated that adult cells can be reprogrammed to iPS cells, there are still challenges associated with this technology:

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and resulted in the live birth of mice derived entirely from iPS cells, thus ending the debate over the equivalence of embryonic stem cells (ESCs) and iPS with regard to pluripotency.

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Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, et al. (December 2007). "Induced pluripotent stem cell lines derived from human somatic cells".

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Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, et al. (July 2007). "In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state".

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Takebe T, Sekine K, Enomura M, Koike H, Kimura M, Ogaeri T, et al. (July 2013). "Vascularized and functional human liver from an iPSC-derived organ bud transplant".

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Aoi T, Yae K, Nakagawa M, Ichisaka T, Okita K, Takahashi K, et al. (August 2008). "Generation of pluripotent stem cells from adult mouse liver and stomach cells".

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Itzhaki I, Maizels L, Huber I, Zwi-Dantsis L, Caspi O, Winterstern A, et al. (March 2011). "Modelling the long QT syndrome with induced pluripotent stem cells".

4381:"Impaired epithelial differentiation of induced pluripotent stem cells from ectodermal dysplasia-related patients is rescued by the small compound APR-246/PRIMA-1MET" 1295:

To make iPSC-based regenerative medicine technologies available to more patients, it is necessary to create universal iPSCs that can be transplanted independently of

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that spontaneously began beating. Cardiomyocytes expressed TnTc, MEF2C, MYL2A, MYHCβ, and NKX2.5. Stem cell-associated genes were downregulated after differentiation.

1180:, can be mass-produced using chemically defined differentiation protocols. These protocols typically modulate the same developmental signaling pathways required for 1133:

of damaged heart without tumor-formation was demonstrated in mice and was successful if the intervention was carried out immediately before or after a heart attack.

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Human iPS cells colonies. The spindle-shaped cells in the background are mouse fibroblast cells. Only those cells comprising the center colony are human iPS cells.

135:. However, since the generation of embryonic stem cells involves destruction (or at least manipulation) of the pre-implantation stage embryo, there has been much 264:

factors, Oct4, Sox2, cMyc, and Klf4, which were each necessary and together sufficient to generate ESC-like colonies under selection for reactivation of Fbx15.

4753:"Human Induced Pluripotent Stem Cell-Derived Cardiac Cell Sheets Expressing Genetically Encoded Voltage Indicator for Pharmacological and Arrhythmia Studies" 3415:

Hou P, Li Y, Zhang X, Liu C, Guan J, Li H, et al. (August 2013). "Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds".

520:: Glis1 is transcription factor that can be used with Oct-3/4, Sox2 and Klf4 to induce pluripotency. It poses numerous advantages when used instead of C-myc. 3899:

Boland MJ, Hazen JL, Nazor KL, Rodriguez AR, Gifford W, Martin G, et al. (September 2009). "Adult mice generated from induced pluripotent stem cells".

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Rais Y, Zviran A, Geula S, Gafni O, Chomsky E, Viukov S, et al. (October 2013). "Deterministic direct reprogramming of somatic cells to pluripotency".

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Zhou T, Benda C, Dunzinger S, Huang Y, Ho JC, Yang J, et al. (December 2012). "Generation of human induced pluripotent stem cells from urine samples".

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Grskovic M, Javaherian A, Strulovici B, Daley GQ (November 2011). "Induced pluripotent stem cells--opportunities for disease modeling and drug discovery".

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are known oncogenes, including the members of the Myc family. While omitting Myc still allows for iPSC formation, the efficiency is reduced up to 100 fold.

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Stem Cell Genes: iPSCs expressed genes expressed in undifferentiated ESCs, including Oct-3/4, Sox2, Nanog, GDF3, REX1, FGF4, ESG1, DPPA2, DPPA4, and hTERT.

292:, a gene that is functionally important in ESCs. By using this different strategy, the researchers created iPSCs that were functionally identical to ESCs. 6205: 952:

Promoter demethylation: Methylation is the transfer of a methyl group to a DNA base, typically the transfer of a methyl group to a cytosine molecule in a

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must be reformatted to that of the target cell type in order to fully reprogram a cell. However, three separate groups were able to find mouse embryonic

2076: 1149:, researchers identified 'vascular progenitor', the high-quality, multipotent vascular stem cells. After the iPS cells were injected directly into the 5136:"Vascular progenitors from cord blood-derived induced pluripotent stem cells possess augmented capacity for regenerating ischemic retinal vasculature" 2797:

Luo M, Ling T, Xie W, Sun H, Zhou Y, Zhu Q, et al. (July 2013). "NuRD blocks reprogramming of mouse somatic cells into pluripotent stem cells".

224:. While this combination is most conventional in producing iPSCs, each of the factors can be functionally replaced by related transcription factors, 4227:"Human induced pluripotent stem cells develop teratoma more efficiently and faster than human embryonic stem cells regardless the site of injection" 508:

expressed in embryonic stem cells and embryonic carcinoma cells associated with differentiation and proliferation. Thomson et al. demonstrated that

4117:"Long-term safety issues of iPSC-based cell therapy in a spinal cord injury model: oncogenic transformation with epithelial-mesenchymal transition" 542:

cell population or in the prolonged culture. However, recently a path was found for efficient reprogramming which required downregulation of the

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The major concern with the potential clinical application of iPSCs is their propensity to form tumors. Much the same as ESC, iPSCs readily form

409:. iPSCs with higher developmental potential could also be generated by enhancing dimerization between Oct4 and Sox2 using a chimeric Sox factor. 6441: 5112: 1202:

In October 2019, a group at Okayama University developed a model of ischemic heart disease using cardiomyocytes differentiated from iPS cells.

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when injected into immunodeficient mice. Teratoma formation is considered a major obstacle to stem-cell based regenerative medicine by the FDA.

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formation, and potency and differentiability, but the full extent of their relation to natural pluripotent stem cells is still being assessed.

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Zhao XY, Li W, Lv Z, Liu L, Tong M, Hai T, et al. (September 2009). "iPS cells produce viable mice through tetraploid complementation".

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Quality of induced pluripotent stem cells is dramatically enhanced by omitting what was thought to be the most crucial reprogramming factor

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injected into laboratory animals with brain lesions were shown to migrate to the lesions and some motor function improvement was observed.

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Incomplete reprogramming: reprogramming also faces the challenge of completeness. This is particularly challenging because the genome-wide

4704:"Monitoring Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes with Genetically Encoded Calcium and Voltage Fluorescent Reporters" 6196: 5900: 624:

in some cases contributes to tumor genesis. Key studies using such strategy were conducted in 2008. Melton et al. studied the effects of

1141:

Embryonic cord-blood cells were induced into pluripotent stem cells using plasmid DNA. Using cell surface endothelial/pericytic markers

1199:

On May 16, 2018, the clinical research plan was approved by the Ministry of Health, Labor and Welfare's expert group with a condition.

4680: 4058:"Grafted human-induced pluripotent stem-cell-derived neurospheres promote motor functional recovery after spinal cord injury in mice" 1546:

Klimanskaya I, Chung Y, Becker S, Lu SJ, Lanza R (November 2006). "Human embryonic stem cell lines derived from single blastomeres".

632:. In 2008, Ding et al. used the inhibition of histone methyl transferase (HMT) with BIX-01294 in combination with the activation of 6446: 1692: 6120:"Transient non-integrative expression of nuclear reprogramming factors promotes multifaceted amelioration of aging in human cells" 731:

agreed to retract both the papers after she was found to have committed 'research misconduct' as concluded in an investigation by

908:; this is unlike other tumors, which typically are of only one cell type. Teratoma formation is a landmark test for pluripotency. 5683:"Development of a model of ischemic heart disease using cardiomyocytes differentiated from human induced pluripotent stem cells" 3656: 672:

Another key strategy for avoiding problems such as tumorgenesis and low throughput has been to use alternate forms of vectors:

5548:"Reengineering an Antiarrhythmic Drug Using Patient hiPSC Cardiomyocytes to Improve Therapeutic Potential and Reduce Toxicity" 5341:"Small-molecule inhibitors of the Wnt pathway potently promote cardiomyocytes from human embryonic stem cell-derived mesoderm" 1192:

the idea of selling cardiomyocytes to pharmaceutical companies and universities to help develop new drugs for heart disease.

277: 4489:"Reduced ciliary polycystin-2 in induced pluripotent stem cells from polycystic kidney disease patients with PKD1 mutations" 644:. demonstrated an alternative to transcription factor reprogramming through the use of drug-like chemicals. By studying the 6267: 3125: 1396: 1323:

system has been reported to suppress the expression of HLA class I and class II, respectively. To avoid NK cell attacks.

117:

could convert somatic cells into pluripotent stem cells. Shinya Yamanaka was awarded the 2012 Nobel Prize along with Sir

6219: 2627: 1271:

where the degenerated RPE tissue was excised. Safety and vision restoration monitoring were to last one to three years.

1188:

and cardiac drug responses, since they exhibit the same genetic background as the patient from which they were derived.

961:

demonstrating their promoter activity and the active promotion and expression of pluripotency-associated genes in iPSCs.

349:

The generation of induced pluripotent cells is crucially dependent on the transcription factors used for the induction.

1303:. The current strategy for the creation of universal iPSCs has two main goals: to remove HLA expression and to prevent 3669: 938:

living mouse pups were created: mice with iPSC derivatives incorporated all across their bodies with 10–90% chimerism.

5185:"Tracking induced pluripotent stem cells-derived neural stem cells in the central nervous system of rats and monkeys" 3722:

Bao X, Zhu X, Liao B, Benda C, Zhuang Q, Pei D, et al. (April 2013). "MicroRNAs in somatic cell reprogramming".

3334:"Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds" 1740:

Eguizabal C, Aran B, Chuva de Sousa Lopes SM, Geens M, Heindryckx B, Panula S, Popovic M, Vassena R, Veiga A (2019).

645: 6008: 3374: 1283:

and that it eliminates the need to use embryonic stem cells. However, these iPSCs were derived from another person.

860:

Pluripotency: iPSCs were capable of differentiation in a fashion similar to ESCs into fully differentiated tissues.

2903:"Switching cell fate: the remarkable rise of induced pluripotent stem cells and lineage reprogramming technologies" 941: 852: 406: 4860:"An Automated Platform for Assessment of Congenital and Drug-Induced Arrhythmia with hiPSC-Derived Cardiomyocytes" 1688: 1218:

were synthesized at the Scottish National Blood Transfusion Service from iPSC. The cells were induced to become a

5498:"High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells" 4803:"High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells" 1100:). This new approach allows different cell types to self-organize into a complex organ, mimicking the process in 314: 2532:"Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells" 1933:

Okita K, Ichisaka T, Yamanaka S (July 2007). "Generation of germline-competent induced pluripotent stem cells".

533:

Low efficiency: in general, the conversion to iPS cells has been incredibly low. For example, the rate at which

6497: 3644: 310: 2080: 1481: 1047:

gene is mutated, display abnormal epithelial commitment that could be partially rescued by a small compound.

140: 6100: 4379:

Shalom-Feuerstein R, Serror L, Aberdam E, Müller FJ, van Bokhoven H, Wiman KG, et al. (February 2013).

3117: 322:

system, while Thomson and colleagues used a different set of factors, Oct4, Sox2, Nanog, and Lin28, using a

5744:

Garber K (September 2015). "RIKEN suspends first clinical trial involving induced pluripotent stem cells".

4225:

Gutierrez-Aranda I, Ramos-Mejia V, Bueno C, Munoz-Lopez M, Real PJ, Mácia A, et al. (September 2010).

2630:

Oct4 is not only unnecessary but damaging during generation of mouse induced pluripotent stem cells (iPSCs)

1425:"Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors" 385: 170:(MyoD) in reprogramming cell fate to a muscle lineage as an important precursor to the discovery of iPSCs. 32: 4968: 6492: 6229:

Allen Cell Explorer – realistic, data-driven 3D visualization of a living hiPSC in its pluri-potent state

5958:"Global trends in clinical trials involving pluripotent stem cells: a systematic multi-database analysis" 388:, and plays a crucial role in maintaining pluripotency. The absence of Oct-3/4 in Oct-3/4 cells, such as 3808:"Chromatin structure and gene expression programs of human embryonic and induced pluripotent stem cells" 3282:"Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds" 2037:"Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution" 1343:

is left unchanged, since the 12 common HLA-C alleles are enough to cover 95% of the world's population.

305:

Reprogramming of human cells to iPSCs was reported in November 2007 by two independent research groups:

5789:"Japan's challenges of translational regenerative medicine: Act on the safety of regenerative medicine" 1264: 701: 3806:

Guenther MG, Frampton GM, Soldner F, Hockemeyer D, Mitalipova M, Jaenisch R, Young RA (August 2010).

893:

after nine weeks. Teratomas are tumors of multiple lineages containing tissue derived from the three

4288: 1467: 964:

DNA methylation globally: Human iPS cells are highly similar to ES cells in their patterns of which

6416: 6260: 6183: 5847: 1391: 1260: 867:, expressing βIII-tubulin, tyrosine hydroxylase, AADC, DAT, ChAT, LMX1B, and MAP2. The presence of 657: 3067:

Woltjen K, Michael IP, Mohseni P, Desai R, Mileikovsky M, Hämäläinen R, et al. (April 2009).

755: 451:

was unnecessary for generation of human iPS cells and in fact failed to generate human iPS cells.

6376: 3466: 3144: 1666: 1324: 1300: 40: 5496:

Sharma A, Burridge PW, McKeithan WL, Serrano R, Shukla P, Sayed N, et al. (February 2017).

5284:"Metabolic Maturation Media Improve Physiological Function of Human iPSC-Derived Cardiomyocytes" 1029:

for both cell lines. Thus, Araki et al. was unable to come to the same conclusion as Zhou et al.

6193: 5904: 5629: 5603: 4283: 4274:

Zhao T, Zhang ZN, Rong Z, Xu Y (May 2011). "Immunogenicity of induced pluripotent stem cells".

2299:"A high-efficiency system for the generation and study of human induced pluripotent stem cells" 1130: 1068:

A proof-of-concept of using induced pluripotent stem cells (iPSCs) to generate human organ for

492: 368: 289: 3171:"A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity" 6426: 6381: 6371: 6355: 6206:

20Minute Video / The Discovery and Future of Induced Pluripotent Stem (iPS) Cells by Yamanaka

2102:

Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (November 2007).

1328: 1244: 1093: 1081: 136: 125: 5390:"Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome" 4702:

Shinnawi R, Huber I, Maizels L, Shaheen N, Gepstein A, Arbel G, et al. (October 2015).

3597:"Adenoviral gene delivery can reprogram human fibroblasts to induced pluripotent stem cells" 911:

Embryoid body: hESCs in culture spontaneously form ball-like embryo-like structures termed "

6131: 5454: 5401: 5339:

Willems E, Spiering S, Davidovics H, Lanier M, Xia Z, Dawson M, et al. (August 2011).

5069: 5018: 4438:

Park IH, Arora N, Huo H, Maherali N, Ahfeldt T, Shimamura A, et al. (September 2008).

4392: 4337: 4173: 4069: 3963: 3908: 3857:"iPS cells can support full-term development of tetraploid blastocyst-complemented embryos" 3424: 3238: 3182: 3080: 3023: 2966: 2859: 2700: 2165: 1993: 1942: 1662: 1555: 1378:, a now-discredited claim of pluripotent stem cell generation by immersing cells in an acid 1312: 1280: 1110: 1089: 1057: 566:

vectors have all been explored, but these often come with the tradeoff of lower throughput.

442: 360: 114: 6085: 6080: 5722: 5655: 5388:

Yazawa M, Hsueh B, Jia X, Pasca AM, Bernstein JA, Hallmayer J, Dolmetsch RE (March 2011).

4115:

Nori S, Okada Y, Nishimura S, Sasaki T, Itakura G, Kobayashi Y, et al. (March 2015).

4056:

Nori S, Okada Y, Yasuda A, Tsuji O, Takahashi Y, Kobayashi Y, et al. (October 2011).

1878:"Safe and stable generation of induced pluripotent stem cells using doggybone DNA vectors" 1382:

Induced pluripotent stem cells vs embryonic stem cells lines obtained by SCNT (discussion)

139:

surrounding their use. Patient-matched embryonic stem cell lines can now be derived using

8: 6487: 6465: 6350: 6290: 6253: 6189:

Generating iPS Cells from MEFS through Forced Expression of Sox-2, Oct-4, c-Myc, and Klf4

6118:

Sarkar TJ, Quarta M, Mukherjee S, Colville A, Paine P, Doan L, et al. (March 2020).

5134:

Park TS, Bhutto I, Zimmerlin L, Huo JS, Nagaria P, Miller D, et al. (January 2014).

1370: 1353: 1308: 818:

Morphology: iPSCs were morphologically similar to ESCs. Each cell had round shape, large

625: 505: 132: 36: 6135: 6084: This article incorporates text from this source, which is available under the 5458: 5405: 5232:

Burridge PW, Matsa E, Shukla P, Lin ZC, Churko JM, Ebert AD, et al. (August 2014).

5073: 5022: 4487:

Freedman BS, Lam AQ, Sundsbak JL, Iatrino R, Su X, Koon SJ, et al. (October 2013).

4396: 4341: 4177: 4073: 3967: 3912: 3572: 3545: 3492:

Lin T, Ambasudhan R, Yuan X, Li W, Hilcove S, Abujarour R, et al. (November 2009).

3428: 3242: 3186: 3084: 3027: 2970: 2863: 2704: 2297:

Maherali N, Ahfeldt T, Rigamonti A, Utikal J, Cowan C, Hochedlinger K (September 2008).

2169: 1997: 1946: 1843: 1714: 1559: 256:. The fibroblasts were engineered so that any cells reactivating the ESC-specific gene, 6228: 6211: 6152: 6119: 6064: 6037: 5984: 5957: 5815: 5788: 5769: 5580: 5547: 5522: 5497: 5478: 5422: 5389: 5365: 5340: 5316: 5283: 5258: 5233: 5209: 5184: 5160: 5135: 5093: 5042: 4984: 4944: 4919: 4894: 4859: 4835: 4802: 4777: 4752: 4751:

Shaheen N, Shiti A, Huber I, Shinnawi R, Arbel G, Gepstein A, et al. (June 2018).

4728: 4703: 4656: 4631: 4612: 4564: 4537: 4513: 4488: 4464: 4439: 4415: 4380: 4361: 4309: 4251: 4226: 4207: 4141: 4116: 4092: 4057: 4033: 4008: 3984: 3952:"Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells" 3951: 3932: 3832: 3807: 3783: 3758: 3626: 3518: 3493: 3448: 3390: 3306: 3281: 3262: 3203: 3170: 3101: 3068: 3044: 3011: 2992: 2927: 2902: 2883: 2832: 2779: 2726: 2605: 2556: 2531: 2512: 2464: 2439: 2415: 2390: 2371: 2323: 2298: 2189: 2035:

Maherali N, Sridharan R, Xie W, Utikal J, Eminli S, Arnold K, et al. (June 2007).

2017: 1966: 1910: 1877: 1852: 1827: 1768: 1741: 1623: 1598: 1579: 1523: 1496: 976:

in size have also been found where iPS cells are not reprogrammed to the ES cell state.

956:(adjacent cytosine/guanine sequence). Widespread methylation of a gene interferes with 935: 796: 5151: 3950:

Lister R, Pelizzola M, Kida YS, Hawkins RD, Nery JR, Hon G, et al. (March 2011).

2581:"Excluding Oct4 from Yamanaka Cocktail Unleashes the Developmental Potential of iPSCs" 2530:

Polo JM, Liu S, Figueroa ME, Kulalert W, Eminli S, Tan KY, et al. (August 2010).

926:, and in the embryoblast, differentiate into the embryo while the blastocyst's shell ( 6421: 6157: 6069: 6038:"Current status and future perspectives of HLA-edited induced pluripotent stem cells" 5989: 5820: 5773: 5761: 5704: 5585: 5567: 5527: 5470: 5427: 5370: 5321: 5303: 5263: 5214: 5165: 5097: 5085: 5034: 4949: 4899: 4881: 4840: 4822: 4782: 4733: 4661: 4604: 4569: 4518: 4469: 4420: 4365: 4353: 4301: 4256: 4199: 4146: 4097: 4038: 3989: 3924: 3878: 3837: 3788: 3739: 3618: 3577: 3523: 3440: 3355: 3311: 3280:

Huangfu D, Maehr R, Guo W, Eijkelenboom A, Snitow M, Chen AE, Melton DA (July 2008).

3266: 3254: 3208: 3106: 3049: 2984: 2932: 2875: 2836: 2824: 2771: 2718: 2669: 2610: 2579:

Velychko S, Adachi K, Kim KP, Hou Y, MacCarthy CM, Wu G, Schöler HR (December 2019).

2561: 2516: 2504: 2469: 2420: 2389:

Staerk J, Dawlaty MM, Gao Q, Maetzel D, Hanna J, Sommer CA, et al. (July 2010).

2375: 2363: 2328: 2279: 2235: 2181: 2135: 2104:"Induction of pluripotent stem cells from adult human fibroblasts by defined factors" 2058: 2009: 1958: 1915: 1897: 1857: 1808: 1773: 1628: 1571: 1528: 1456: 1386: 1181: 1101: 1097: 539: 534: 455:

and Klf4 were found to be factors capable of generating iPS cells, and related genes

4988: 4211: 3695: 3630: 3452: 3394: 2996: 2730: 2193: 1583: 1109:

longevity of the transplanted organ in the host body (ability to integrate or avoid

871:-associated enzymes may indicate that iPSCs, like hESCs, may be differentiable into 335:

blood cells, and in 2012, iPSCs were made from renal epithelial cells in the urine.

6386: 6300: 6147: 6139: 6059: 6049: 5979: 5969: 5810: 5800: 5753: 5694: 5575: 5559: 5517: 5509: 5482: 5462: 5417: 5409: 5360: 5352: 5311: 5295: 5253: 5245: 5204: 5196: 5155: 5147: 5077: 5046: 5026: 4976: 4939: 4931: 4889: 4871: 4830: 4814: 4772: 4764: 4723: 4715: 4651: 4643: 4616: 4596: 4559: 4549: 4508: 4500: 4459: 4451: 4410: 4400: 4345: 4313: 4293: 4246: 4238: 4189: 4181: 4136: 4128: 4087: 4077: 4028: 4020: 3979: 3971: 3936: 3916: 3868: 3827: 3819: 3778: 3770: 3731: 3608: 3567: 3557: 3513: 3505: 3432: 3382: 3345: 3301: 3293: 3246: 3198: 3190: 3169:

Marión RM, Strati K, Li H, Murga M, Blanco R, Ortega S, et al. (August 2009).

3096: 3088: 3039: 3031: 2974: 2922: 2914: 2887: 2867: 2814: 2806: 2783: 2761: 2753: 2708: 2659: 2600: 2592: 2551: 2543: 2496: 2459: 2451: 2410: 2402: 2355: 2318: 2310: 2269: 2225: 2173: 2125: 2115: 2048: 2021: 2001: 1950: 1905: 1889: 1847: 1839: 1800: 1763: 1753: 1618: 1610: 1563: 1518: 1508: 1446: 1436: 1275: 1165: 1076:

buds' (iPSC-LBs) were grown from a mixture of three different kinds of stem cells:

1069: 886: 249: 163: 5356: 4009:"Deconstructing stem cell tumorigenicity: a roadmap to safe regenerative medicine" 2918: 2713: 2688: 1970: 1828:"Research on induced pluripotent stem cells and the application in ocular tissues" 97:, who together showed in 2006 that the introduction of four specific genes (named 6367: 6295: 6240: 6223: 6200: 6188: 5513: 5299: 4818: 4768: 4719: 4132: 3069:"piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells" 2648:"Highly cooperative chimeric super-SOX induces naive pluripotency across species" 2391:"Reprogramming of human peripheral blood cells to induced pluripotent stem cells" 1150: 969: 957: 784: 633: 578: 306: 245: 121:"for the discovery that mature cells can be reprogrammed to become pluripotent." 86: 39:

of a colony of human induced pluripotent stem cells derived from a patient with

6009:"What are induced pluripotent stem cells or IPS cells & clinical prospects?" 5927:"First serious adverse reaction to iPS-derived retinal cell transplant reported" 2258:"Guidelines and techniques for the generation of induced pluripotent stem cells" 1791:

Yamanaka S (December 2013). "The winding road to pluripotency (Nobel Lecture)".

6436: 6431: 6398: 6143: 6054: 5974: 5805: 5699: 5682: 5563: 4935: 4554: 4455: 4385:

Proceedings of the National Academy of Sciences of the United States of America

4062:

Proceedings of the National Academy of Sciences of the United States of America

3873: 3856: 3823: 3562: 3350: 3333: 2664: 2647: 2596: 2455: 2438:

Loh YH, Hartung O, Li H, Guo C, Sahalie JM, Manos PD, et al. (July 2010).

2406: 2314: 2274: 2257: 2230: 2213: 2120: 2103: 2053: 2036: 1893: 1614: 1441: 1424: 1236: 1215: 879: 848: 620: 4980: 3735: 3386: 600: 272:

In June 2007, three separate research groups, including that of Yamanaka's, a

6481: 6216: 5873: 5571: 5307: 4885: 4876: 4826: 2580: 1901: 1177: 1126: 934:

into a trophoblast, and the blastocyst was transferred to recipient females.

912: 875:

neurons. Stem cell-associated genes were downregulated after differentiation.

868: 788: 619:

One of the main strategies for avoiding problems (1) and (2) has been to use

472: 233: 179: 5787:

Tobita M, Konomi K, Torashima Y, Kimura K, Taoka M, Kaminota M (June 2016).

5081: 4405: 4185: 4082: 3436: 3035: 2979: 2954: 2687:

Ali PS, Ghoshdastider U, Hoffmann J, Brutschy B, Filipek S (November 2012).

2177: 1758: 1196:

application with the Ministry of Health, Labor and Welfare on the same day.

660:

was sufficient to induce pluripotency. The acronym given for those iPSCs is

6315: 6217:

University of Oxford practical workshop on pluripotent stem cell technology

6161: 6073: 5993: 5824: 5765: 5708: 5589: 5531: 5474: 5431: 5374: 5325: 5267: 5218: 5200: 5169: 5089: 5038: 4953: 4903: 4844: 4786: 4737: 4665: 4608: 4573: 4522: 4504: 4473: 4424: 4357: 4305: 4260: 4224: 4203: 4150: 4101: 4042: 3993: 3928: 3882: 3841: 3792: 3743: 3622: 3581: 3527: 3444: 3359: 3315: 3258: 3212: 3110: 3053: 2988: 2936: 2879: 2828: 2775: 2722: 2673: 2614: 2565: 2508: 2500: 2473: 2424: 2367: 2332: 2283: 2239: 2185: 2139: 2062: 2013: 1962: 1919: 1861: 1812: 1804: 1777: 1632: 1575: 1532: 1513: 1497:"Stem Cells Applications in Regenerative Medicine and Disease Therapeutics" 1460: 1158: 1085: 931: 872: 82: 55: 48: 2955:"Generation of mouse induced pluripotent stem cells without viral vectors" 4647: 3546:"Generation of induced pluripotent stem cells using recombinant proteins" 3010:

Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K (November 2008).

2953:

Okita K, Nakagawa M, Hyenjong H, Ichisaka T, Yamanaka S (November 2008).

1157:

of mice, the stem cells engrafted into the retina, grew and repaired the

927: 919: 649: 512:

is a factor in iPSC generation in combination with OCT4, SOX2, and NANOG.

393: 196: 184: 118: 75: 6101:"Anti-Aging Stem Cell Treatment Proves Successful in Early Human Trials" 5757: 5466: 5413: 5030: 4349: 4297: 3975: 3920: 3250: 3194: 3092: 2871: 2757: 2005: 1954: 1567: 811:

and pluripotency of iPSCs to naturally isolated pluripotent stem cells:

488:

have been identified to induce instead of c-myc with similar efficiency.

309:

of Kyoto University, Japan, who pioneered the original iPSC method, and

155:

Yamanaka named iPSCs with a lower case "i" due to the popularity of the

6184:

With few factors, adult cells take on character of embryonic stem cells

5249: 5183:

Tang H, Sha H, Sun H, Wu X, Xie L, Wang P, et al. (October 2013).

4194: 3509: 3332:

Shi Y, Desponts C, Do JT, Hahm HS, Schöler HR, Ding S (November 2008).

2819: 2766: 2155: 1874: 1451: 1240: 1223: 1185: 1077: 923: 894: 844: 673: 589: 586: 582: 563: 559: 543: 389: 323: 319: 253: 148: 5903:. RIKEN Center for Developmental Biology. 4 April 2017. Archived from 2810: 2640: 2638: 2636: 2130: 1739: 707: 6276: 4242: 3774: 3759:"Embryonic stem cell-specific microRNAs promote induced pluripotency" 3613: 3596: 2547: 2359: 2214:"Patient-specific pluripotent stem cells become even more accessible" 1296: 1256: 973: 823: 819: 768: 413: 356: 78: 4600: 4378: 4024: 3544:

Zhou H, Wu S, Joo JY, Zhu S, Han DW, Lin T, et al. (May 2009).

3297: 3012:"Induced pluripotent stem cells generated without viral integration" 1267:(RPE) cells. The cell sheet would be transplanted into the affected 524: 6178: 5878: 2633: 1219: 1025: 1021: 997: 965: 953: 905: 901: 897: 890: 807: 792: 776: 772: 764: 743: 571: 477: 225: 200: 189:

A scheme of the generation of induced pluripotent stem (IPS) cells.

5901:"First donor iPSC-derived RPE cell transplantation in AMD patient" 5837: 918:

Chimeric mice: hESCs naturally reside within the inner cell mass (

5544: 4586: 3805: 2743: 2644: 1304: 980: 830: 803: 728: 677: 614: 555: 380: 352: 273: 192: 162:

In his Nobel seminar, Yamanaka cited the earlier seminal work of

4632:"Induced pluripotent stem cell technology: a decade of progress" 4538:"The human brain in a dish: the promise of iPSC-derived neurons" 2686: 1482:"The Nobel Prize in Physiology or Medicine – 2012 Press Release" 199:(lightgray). (4) A small subset of the transfected cells become 6338: 6328: 5338: 5113:"Researchers repair retinas in mice with virus-free stem cells" 1268: 1212: 1154: 864: 760: 398: 6194:

2 Minute Video from BSCRF about Induced Pluripotent Stem Cells

6179:

Center for iPS Cell Research and Application, Kyoto University

5495: 5444: 5280: 4799: 3670:"Japan researcher agrees to withdraw disputed stem cell paper" 2296: 1983: 6333: 6245: 6117: 5723:"First transfusions of "manufactured" blood planned for 2016" 5681:

Wei H, Wang C, Guo R, Takahashi K, Naruse K (December 2019).

4857: 2952: 1340: 1332: 1316: 1248: 1146: 1114: 1073: 732: 516: 509: 500: 485: 481: 434: 430: 375:, have been identified to increase the induction efficiency. 372: 257: 209: 102: 94: 90: 44: 4920:"A deep learning platform to assess drug proarrhythmia risk" 1742:"Two decades of embryonic stem cells: a historical overview" 27:

Pluripotent stem cell generated directly from a somatic cell

5786: 4916: 4701: 3756: 3494:"A chemical platform for improved induction of human iPSCs" 3279: 2689:"Recognition of the let-7g miRNA precursor by human Lin28B" 2101: 1336: 1320: 1252: 1142: 1044: 855:), a necessary component in the telomerase protein complex. 847:

are necessary to sustain cell division unrestricted by the

697: 693: 689: 629: 547: 460: 456: 452: 447: 426: 422: 418: 402: 217: 213: 167: 156: 110: 106: 5059: 4681:"Roche, Pfizer, Sanofi Plan $ 72.7 Million Stem-Cell Bank" 4486: 3949: 3467:"Major Step In Making Better Stem Cells From Adult Tissue" 3066: 2034: 425:

yields iPSCs with a similar efficiency as Sox2, and genes

5956:

Deinsberger J, Reisinger D, Weber B (11 September 2020).

5955: 4750: 3898: 3009: 2900: 1290: 759:

Three germ line cells/tissues differentiated from iPSCs:

467: 364: 281: 221: 131:

The most well-known type of pluripotent stem cell is the

98: 5008: 4114: 3757:

Judson RL, Babiarz JE, Venere M, Blelloch R (May 2009).

2901:

Selvaraj V, Plane JM, Williams AJ, Deng W (April 2010).

1545: 1050: 878:

Cardiac differentiation: iPSCs were differentiated into

329: 5234:"Chemically defined generation of human cardiomyocytes" 3126:"Cancer threat removed from stem cells, scientists say" 2529: 2486: 2388: 2345: 863:

Neural differentiation: iPSCs were differentiated into

295: 244:

Induced pluripotent stem cells were first generated by

5231: 5133: 4163: 2440:"Reprogramming of T cells from human peripheral blood" 1882:

Molecular Therapy - Methods & Clinical Development

1639: 3855:

Kang L, Wang J, Zhang Y, Kou Z, Gao S (August 2009).

1932: 1184:. These iPSC-cardiomyocytes can recapitulate genetic 5874:"Pioneering adult stem cell trial approved by Japan" 4437: 4326: 4055: 2849: 2578: 2255: 1599:"Induced Pluripotent Stem Cells Meet Genome Editing" 585:(MEF)-derived iPS cells that could be injected into 300: 124:

Pluripotent stem cells hold promise in the field of

113:), collectively known as Yamanaka factors, encoding 5687:

Biochemical and Biophysical Research Communications

5680: 5387: 4630:Shi Y, Inoue H, Wu JC, Yamanaka S (February 2017). 3491: 3168: 1376:

Stimulus-triggered acquisition of pluripotency cell

708:

Stimulus-triggered acquisition of pluripotency cell

4629: 4535: 3696:"Report on STAP Cell Research Paper Investigation" 3643:David Cyranoski for Nature News. January 29, 2014 1596: 4440:"Disease-specific induced pluripotent stem cells" 3331: 1422: 525:Challenges in reprogramming cells to pluripotency 6479: 5780: 3854: 260:, could be isolated using antibiotic selection. 4273: 3894: 3892: 3721: 3539: 3537: 3375:"Stem cells reprogrammed using chemicals alone" 3327: 3325: 3224: 3222: 2948: 2946: 2437: 2151: 2149: 1072:was reported by researchers from Japan. Human ' 1020:equivalent ES cells however, Zhou et al. found 392:and embryonic stem cells, leads to spontaneous 6442:Stem cell laws and policy in the United States 6035: 5867: 5865: 3655:Tracy Vence for the Scientist. March 11, 2014 3459: 721:stimulus-triggered acquisition of pluripotency 714:Stimulus-triggered acquisition of pluripotency 615:Mimicking transcription factors with chemicals 471:: The Myc family of transcription factors are 463:did as well, although with reduced efficiency. 342: 6261: 6111: 6031: 6029: 4493:Journal of the American Society of Nephrology 3693: 3414: 2796: 2251: 2249: 2207: 2205: 2203: 2077:"Generations of iPSCs and related references" 5737: 5182: 5176: 5127: 5002: 4695: 4580: 4480: 4431: 4372: 4320: 4267: 4218: 4157: 3889: 3543: 3534: 3485: 3408: 3322: 3273: 3219: 3162: 3060: 3003: 2943: 2894: 2843: 2790: 2737: 2680: 2523: 2480: 2431: 2382: 2290: 2256:Maherali N, Hochedlinger K (December 2008). 2146: 2095: 2028: 1977: 1926: 1707: 1651: 1418: 1416: 1414: 1412: 1012:thought to be safer than retroviral methods. 267: 5862: 3228: 3145:"Stem Cells – This Time Without the Cancer" 3142: 3136: 1590: 1539: 1488: 1176:Beating cardiac muscle cells, iPSC-derived 239: 6268: 6254: 6026: 2246: 2200: 1819: 664:(protein-induced pluripotent stem cells). 6151: 6063: 6053: 6006: 5983: 5973: 5871: 5814: 5804: 5698: 5579: 5521: 5421: 5364: 5315: 5257: 5208: 5159: 4943: 4893: 4875: 4834: 4776: 4727: 4655: 4563: 4553: 4512: 4463: 4414: 4404: 4287: 4250: 4193: 4140: 4091: 4081: 4032: 4006: 3983: 3872: 3831: 3782: 3612: 3594: 3571: 3561: 3517: 3372: 3349: 3305: 3202: 3100: 3043: 2978: 2926: 2818: 2765: 2712: 2663: 2604: 2555: 2463: 2414: 2339: 2322: 2273: 2229: 2129: 2119: 2052: 1909: 1851: 1767: 1757: 1622: 1522: 1512: 1450: 1440: 1409: 609: 384:(Pou5f1) Oct-3/4 is one of the family of 6447:Epigenetics in stem cell differentiation 5838:Riken Center for Developmental Biology. 3645:Acid bath offers easy path to stem cells 2211: 1790: 1645: 1346: 1263:were reprogrammed to differentiate into 1080:(for liver function) coaxed from iPSCs; 885:Teratoma formation: iPSCs injected into 754: 599: 183: 54: 47:, green the protein SSEA4, and blue the 31: 3661: 1825: 1681: 1423:Takahashi K, Yamanaka S (August 2006). 1247:and was to be conducted in 2014 at the 1125:In 2021, a switchable Yamanaka factors- 195:culture, using mitotically inactivated 85:. The iPSC technology was pioneered by 14: 6480: 6098: 5743: 5110: 4678: 4536:Dolmetsch R, Geschwind D (June 2011). 3123: 1832:International Journal of Ophthalmology 1715:"山中教授の「iPS細胞」ってiPod のパクリ!?流行らせたいと頭小文字" 1291:Strategy for obtaining universal iPSCs 1249:Riken Center for Developmental Biology 680:, and naked DNA or protein compounds. 81:that can be generated directly from a 6249: 4969:"Miniature human liver grown in mice" 4966: 3717: 3715: 3713: 1597:Hockemeyer D, Jaenisch R (May 2016). 1501:International Journal of Cell Biology 1494: 1120: 1113:) and whether it will transform into 1051:Disease modeling and drug development 829:Growth properties: Doubling time and 386:octamer ("Oct") transcription factors 330:Generation from additional cell types 278:University of California, Los Angeles 43:. Red indicates transcription factor 5656:"ｉＰＳ細胞の心筋シート移植、臨床研究を国が大筋了承：朝日新聞デジタル" 3667: 1261:wet age-related macular degeneration 667: 296:Human induced pluripotent stem cells 1844:10.3980/j.issn.2222-3959.2015.04.31 1033: 24: 3710: 3595:Zhou W, Freed CR (November 2009). 3143:Swaminathan N (30 November 2007). 1205: 1063: 363:(Klf1, Klf2, Klf4, and Klf5), the 25: 6509: 6172: 6036:Koga K, Wang B, Kaneko S (2020). 5933:. 17 January 2018. Archived from 5152:10.1161/CIRCULATIONAHA.113.003000 1484:. Nobel Media AB. 8 October 2012. 1230: 1171: 775:) and goblet cells in intestine ( 646:mesenchymal-epithelial transition 407:tetraploid embryo complementation 301:Generation from human fibroblasts 6460: 6459: 6092: 6079: 6000: 5949: 5919: 5893: 5831: 1665:. 8 October 2012. Archived from 1466: 1136: 853:telomerase reverse transcriptase 802:Gene expression and genome-wide 738: 168:myoblast determination protein 1 6007:Knoepfler P (25 January 2021). 5715: 5674: 5648: 5622: 5596: 5538: 5489: 5438: 5381: 5332: 5274: 5225: 5104: 5053: 4960: 4910: 4851: 4793: 4744: 4672: 4623: 4529: 4108: 4049: 4000: 3943: 3848: 3799: 3750: 3724:Current Opinion in Cell Biology 3687: 3649: 3637: 3588: 3366: 2621: 2572: 2069: 1868: 1784: 1733: 815:Cellular biological properties 315:University of Wisconsin-Madison 6306:Induced pluripotent stem cells 6275: 5502:Science Translational Medicine 4807:Science Translational Medicine 4589:Nature Reviews. Drug Discovery 3694:Press Release (1 April 2014). 1474: 546:remodeling and deacetylation ( 280:collaboration, and a group at 203:and generate ES-like colonies. 64:Induced pluripotent stem cells 18:Induced pluripotent stem cells 13: 1: 6042:Inflammation and Regeneration 5357:10.1161/CIRCRESAHA.111.249540 2919:10.1016/j.tibtech.2010.01.002 2714:10.1016/j.febslet.2012.09.034 1402: 1331:inhibiting NK-cells, such as 1274:In March 2017, a team led by 173: 141:somatic cell nuclear transfer 6099:Haridy R (23 October 2017). 5872:Gallagher J (19 July 2013). 5514:10.1126/scitranslmed.aaf2584 5300:10.1016/j.celrep.2020.107925 5111:Mullin E (28 January 2014). 4819:10.1126/scitranslmed.aaf2584 4769:10.1016/j.stemcr.2018.04.006 4720:10.1016/j.stemcr.2015.08.009 4679:Gerlin A (5 December 2012). 4133:10.1016/j.stemcr.2015.01.006 3373:Cyranoski D (18 July 2013). 355:and certain products of the 7: 6212:Fact sheet on reprogramming 5725:. Gizmag.com. 23 April 2014 5610:(in Japanese). 24 June 2014 1689:"万能なiPS細胞「iPodのように普及してほしい」" 1359: 750: 367:(c-myc, L-myc, and N-myc), 343:Genes used to produce iPSCs 248:and Kazutoshi Takahashi at 89:and Kazutoshi Takahashi in 10: 6514: 6144:10.1038/s41467-020-15174-3 6055:10.1186/s41232-020-00132-9 5975:10.1038/s41536-020-00100-4 5806:10.1016/j.reth.2016.04.001 5700:10.1016/j.bbrc.2019.09.119 5662:(in Japanese). 16 May 2018 5636:(in Japanese). 16 May 2018 5604:"iPSから心筋細胞製造タカラバイオとベンチャー" 5564:10.1016/j.stem.2020.08.003 4936:10.1016/j.stem.2022.12.002 4555:10.1016/j.cell.2011.05.034 4456:10.1016/j.cell.2008.07.041 3874:10.1016/j.stem.2009.07.001 3824:10.1016/j.stem.2010.06.015 3563:10.1016/j.stem.2009.04.005 3351:10.1016/j.stem.2008.10.004 2665:10.1016/j.stem.2023.11.010 2597:10.1016/j.stem.2019.10.002 2456:10.1016/j.stem.2010.06.004 2407:10.1016/j.stem.2010.06.002 2315:10.1016/j.stem.2008.08.003 2275:10.1016/j.stem.2008.11.008 2231:10.1016/j.stem.2010.06.009 2121:10.1016/j.cell.2007.11.019 2054:10.1016/j.stem.2007.05.014 1894:10.1016/j.omtm.2021.09.018 1615:10.1016/j.stem.2016.04.013 1442:10.1016/j.cell.2006.07.024 1265:retinal pigment epithelial 1243:iPSCs was approved by the 942:Tetraploid complementation 889:mice spontaneously formed 711: 702:PiggyBac Transposon System 177: 37:Confocal microscopic image 6455: 6409: 6314: 6283: 6234:CamBioScience iPSC course 5962:npj Regenerative Medicine 4981:10.1038/nature.2013.13324 4007:Knoepfler PS (May 2009). 3736:10.1016/j.ceb.2012.12.004 3657:Call for STAP Retractions 3387:10.1038/nature.2013.13416 3124:Kaplan K (6 March 2009). 1659:"「i」PSなぜ小文字？山中さんってどんな人？" 990: 949:Epigenetic reprogramming 787:patterns, doubling time, 688:the other three factors ( 268:Second generation (mouse) 6417:Cellular differentiation 5630:"iPSで心臓治療了承高難度の再生医療へ一歩" 4877:10.3389/fphys.2017.00766 3149:Scientific American News 2212:Yamanaka S (July 2010). 1826:Guo XL, Chen JS (2015). 1392:Directed differentiation 1311:of HLA. Deletion of the 240:First generation (mouse) 6377:Hematopoietic stem cell 5082:10.1126/science.abg5159 4967:Baker M (3 July 2013). 4864:Frontiers in Physiology 4406:10.1073/pnas.1201753109 4186:10.1126/science.1154884 4083:10.1073/pnas.1108077108 3437:10.1126/science.1239278 3036:10.1126/science.1162494 2980:10.1126/science.1164270 2907:Trends in Biotechnology 2178:10.1126/science.1151526 1746:Human Reproduction Open 1259:from six patients with 1164:Labelled iPSCs-derived 979:Histone demethylation: 41:oculocutaneous albinism 5931:The Japan Times Online 5201:10.1089/cell.2012.0081 5189:Cellular Reprogramming 4505:10.1681/ASN.2012111089 3668:Lies E (4 June 2014). 2501:10.1038/nprot.2012.115 1805:10.1002/anie.201306721 1094:mesenchymal stem cells 1082:endothelial stem cells 780: 610:Alternative approaches 606: 204: 60: 52: 6498:2006 in biotechnology 6427:Stem cell controversy 6382:Mesenchymal stem cell 6372:Endothelial stem cell 6239:23 April 2019 at the 6199:18 April 2011 at the 6124:Nature Communications 1759:10.1093/hropen/hoy024 1347:Anti-aging properties 1245:Japan Ministry Health 843:Telomerase activity: 785:chromatin methylation 758: 658:poly-arginine anchors 603: 187: 126:regenerative medicine 115:transcription factors 58: 35: 6291:Embryonic stem cells 6222:8 April 2016 at the 5793:Regenerative Therapy 5746:Nature Biotechnology 5345:Circulation Research 4648:10.1038/nrd.2016.245 3763:Nature Biotechnology 3286:Nature Biotechnology 2536:Nature Biotechnology 2348:Nature Biotechnology 1514:10.1155/2016/6940283 1371:Stem cell treatments 1129:-based approach for 1090:umbilical cord blood 1058:University of Oxford 506:mRNA binding protein 159:and other products. 6351:Embryonic stem cell 6136:2020NatCo..11.1545S 5907:on 6 September 2017 5758:10.1038/nbt0915-890 5467:10.1038/nature09747 5459:2011Natur.471..225I 5414:10.1038/nature09855 5406:2011Natur.471..230Y 5115:. fiercebiotech.com 5074:2021Sci...373.1537C 5068:(6562): 1537–1540. 5031:10.1038/nature12271 5023:2013Natur.499..481T 4636:Nat Rev Drug Discov 4397:2013PNAS..110.2152S 4350:10.1038/nature11807 4342:2013Natur.494..100A 4298:10.1038/nature10135 4178:2008Sci...321..699A 4074:2011PNAS..10816825N 3976:10.1038/nature09798 3968:2011Natur.471...68L 3921:10.1038/nature08310 3913:2009Natur.461...91B 3429:2013Sci...341..651H 3251:10.1038/nature08267 3243:2009Natur.461...86Z 3195:10.1038/nature08287 3187:2009Natur.460.1149M 3093:10.1038/nature07863 3085:2009Natur.458..766W 3028:2008Sci...322..945S 2971:2008Sci...322..949O 2872:10.1038/nature12587 2864:2013Natur.502...65R 2758:10.1038/nature10106 2705:2012FEBSL.586.3986S 2170:2007Sci...318.1917Y 2006:10.1038/nature05944 1998:2007Natur.448..318W 1955:10.1038/nature05934 1947:2007Natur.448..313O 1669:on 21 November 2012 1568:10.1038/nature05142 1560:2006Natur.444..481K 1354:Stanford University 1084:(to form lining of 626:histone deacetylase 133:embryonic stem cell 49:nuclei of the cells 6493:Induced stem cells 5937:on 27 January 2018 5250:10.1038/nmeth.2999 3510:10.1038/nmeth.1393 1366:Induced stem cells 1121:Organ regeneration 795:formation, viable 781: 607: 205: 152:basis of disease. 61: 53: 6475: 6474: 6422:Stem cell therapy 6301:Cancer stem cells 5558:(5): 813–821.e6. 5508:(377): eaaf2584. 4813:(377): eaaf2584. 4757:Stem Cell Reports 4708:Stem Cell Reports 4172:(5889): 699–702. 4121:Stem Cell Reports 3473:. 19 October 2009 3181:(7259): 1149–53. 3130:Los Angeles Times 2811:10.1002/stem.1374 2658:(1): 127–147.e9. 2591:(6): 737–753.e4. 2164:(5858): 1917–20. 1793:Angewandte Chemie 1495:Mahla RS (2016). 1387:Dedifferentiation 1182:heart development 1102:fetal development 1098:connective tissue 735:on 1 April 2014. 668:Alternate vectors 16:(Redirected from 6505: 6463: 6462: 6410:Related articles 6387:Neural stem cell 6296:Adult stem cells 6270: 6263: 6256: 6247: 6246: 6166: 6165: 6155: 6115: 6109: 6108: 6096: 6090: 6083: 6077: 6067: 6057: 6033: 6024: 6023: 6021: 6019: 6004: 5998: 5997: 5987: 5977: 5953: 5947: 5946: 5944: 5942: 5923: 5917: 5916: 5914: 5912: 5897: 5891: 5890: 5888: 5886: 5869: 5860: 5859: 5857: 5855: 5846:. 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After growing 1034:Medical research 634:calcium channels 250:Kyoto University 164:Harold Weintraub 74:) are a type of 21: 6513: 6512: 6508: 6507: 6506: 6504: 6503: 6502: 6478: 6477: 6476: 6471: 6451: 6405: 6368:Progenitor cell 6310: 6279: 6274: 6241:Wayback Machine 6224:Wayback Machine 6208:January 8, 2008 6201:Wayback Machine 6175: 6170: 6169: 6116: 6112: 6097: 6093: 6034: 6027: 6017: 6015: 6005: 6001: 5954: 5950: 5940: 5938: 5925: 5924: 5920: 5910: 5908: 5899: 5898: 5894: 5884: 5882: 5870: 5863: 5853: 5851: 5850:on 26 June 2013 5836: 5832: 5785: 5781: 5742: 5738: 5728: 5726: 5721: 5720: 5716: 5679: 5675: 5665: 5663: 5654: 5653: 5649: 5639: 5637: 5628: 5627: 5623: 5613: 5611: 5602: 5601: 5597: 5543: 5539: 5494: 5490: 5453:(7337): 225–9. 5443: 5439: 5400:(7337): 230–4. 5386: 5382: 5337: 5333: 5279: 5275: 5230: 5226: 5181: 5177: 5132: 5128: 5118: 5116: 5109: 5105: 5058: 5054: 5017:(7459): 481–4. 5007: 5003: 4993: 4991: 4965: 4961: 4930:(1): 86–95.e4. 4915: 4911: 4856: 4852: 4798: 4794: 4749: 4745: 4700: 4696: 4686: 4684: 4683:. Bloomberg.com 4677: 4673: 4628: 4624: 4601:10.1038/nrd3577 4585: 4581: 4534: 4530: 4499:(10): 1571–86. 4485: 4481: 4436: 4432: 4377: 4373: 4336:(7435): 100–4. 4325: 4321: 4289:10.1.1.864.8029 4282:(7350): 212–5. 4272: 4268: 4223: 4219: 4162: 4158: 4113: 4109: 4054: 4050: 4025:10.1002/stem.37 4005: 4001: 3962:(7336): 68–73. 3948: 3944: 3897: 3890: 3853: 3849: 3804: 3800: 3755: 3751: 3720: 3711: 3701: 3699: 3692: 3688: 3678: 3676: 3666: 3662: 3654: 3650: 3642: 3638: 3607:(11): 2667–74. 3593: 3589: 3542: 3535: 3490: 3486: 3476: 3474: 3465: 3464: 3460: 3423:(6146): 651–4. 3413: 3409: 3399: 3397: 3371: 3367: 3330: 3323: 3298:10.1038/nbt1418 3278: 3274: 3237:(7260): 86–90. 3227: 3220: 3167: 3163: 3153: 3151: 3141: 3137: 3122: 3118: 3065: 3061: 3022:(5903): 945–9. 3008: 3004: 2951: 2944: 2899: 2895: 2858:(7469): 65–70. 2848: 2844: 2795: 2791: 2752:(7350): 225–9. 2742: 2738: 2699:(22): 3986–90. 2685: 2681: 2643: 2634: 2626: 2622: 2577: 2573: 2528: 2524: 2485: 2481: 2436: 2432: 2387: 2383: 2354:(11): 1276–84. 2344: 2340: 2295: 2291: 2254: 2247: 2210: 2201: 2154: 2147: 2100: 2096: 2086: 2084: 2083:on 30 June 2018 2075: 2074: 2070: 2033: 2029: 1982: 1978: 1941:(7151): 313–7. 1931: 1927: 1873: 1869: 1824: 1820: 1799:(52): 13900–9. 1789: 1785: 1738: 1734: 1724: 1722: 1713: 1712: 1708: 1698: 1696: 1687: 1686: 1682: 1672: 1670: 1657: 1656: 1652: 1644: 1640: 1595: 1591: 1554:(7118): 481–5. 1544: 1540: 1493: 1489: 1480: 1479: 1475: 1465: 1421: 1410: 1405: 1362: 1349: 1339:has been used. 1307:attacks due to 1293: 1233: 1216:red blood cells 1208: 1206:Red blood cells 1174: 1153:of the damaged 1139: 1123: 1070:transplantation 1066: 1064:Organ synthesis 1053: 1036: 993: 913:embryoid bodies 887:immunodeficient 753: 741: 716: 710: 670: 621:small molecules 617: 612: 579:epigenetic code 527: 473:proto-oncogenes 357:Sox gene family 345: 332: 307:Shinya Yamanaka 303: 298: 270: 246:Shinya Yamanaka 242: 182: 176: 166:on the role of 87:Shinya Yamanaka 66:(also known as 28: 23: 22: 15: 12: 11: 5: 6511: 6501: 6500: 6495: 6490: 6473: 6472: 6470: 6469: 6456: 6453: 6452: 6450: 6449: 6444: 6439: 6437:Stem cell laws 6434: 6432:Stem cell line 6429: 6424: 6419: 6413: 6411: 6407: 6406: 6404: 6403: 6402: 6401: 6399:Precursor cell 6391: 6390: 6389: 6384: 6379: 6374: 6360: 6359: 6358: 6353: 6343: 6342: 6341: 6336: 6331: 6320: 6318: 6312: 6311: 6309: 6308: 6303: 6298: 6293: 6287: 6285: 6281: 6280: 6273: 6272: 6265: 6258: 6250: 6244: 6243: 6231: 6226: 6214: 6209: 6203: 6191: 6186: 6181: 6174: 6173:External links 6171: 6168: 6167: 6110: 6091: 6025: 5999: 5948: 5918: 5892: 5861: 5830: 5779: 5736: 5714: 5693:(3): 600–605. 5673: 5647: 5621: 5595: 5552:Cell Stem Cell 5537: 5488: 5437: 5380: 5331: 5273: 5238:Nature Methods 5224: 5175: 5126: 5103: 5052: 5001: 4959: 4924:Cell Stem Cell 4909: 4850: 4792: 4743: 4694: 4671: 4622: 4595:(12): 915–29. 4579: 4528: 4479: 4430: 4371: 4319: 4266: 4237:(9): 1568–70. 4217: 4156: 4107: 4048: 3999: 3942: 3907:(7260): 91–4. 3888: 3861:Cell Stem Cell 3847: 3812:Cell Stem Cell 3798: 3749: 3709: 3686: 3660: 3648: 3636: 3587: 3550:Cell Stem Cell 3533: 3498:Nature Methods 3484: 3458: 3407: 3365: 3338:Cell Stem Cell 3321: 3272: 3218: 3161: 3135: 3116: 3059: 3002: 2942: 2893: 2842: 2805:(7): 1278–86. 2789: 2736: 2679: 2652:Cell Stem Cell 2632: 2620: 2585:Cell Stem Cell 2571: 2522: 2495:(12): 2080–9. 2479: 2444:Cell Stem Cell 2430: 2395:Cell Stem Cell 2381: 2338: 2303:Cell Stem Cell 2289: 2268:(6): 595–605. 2262:Cell Stem Cell 2245: 2218:Cell Stem Cell 2199: 2145: 2094: 2068: 2041:Cell Stem Cell 2027: 1976: 1925: 1867: 1818: 1783: 1732: 1706: 1680: 1650: 1648:, p. 120. 1638: 1603:Cell Stem Cell 1589: 1538: 1487: 1473: 1407: 1406: 1404: 1401: 1400: 1399: 1394: 1389: 1384: 1379: 1373: 1368: 1361: 1358: 1348: 1345: 1292: 1289: 1237:clinical trial 1232: 1231:Clinical trial 1229: 1207: 1204: 1178:cardiomyocytes 1173: 1172:Cardiomyocytes 1170: 1138: 1135: 1122: 1119: 1065: 1062: 1052: 1049: 1035: 1032: 1031: 1030: 1017: 1013: 1009: 1005: 1001: 992: 989: 988: 987: 986: 985: 977: 962: 947: 946: 945: 939: 916: 909: 883: 880:cardiomyocytes 876: 858: 857: 856: 849:Hayflick limit 841: 838: 834: 827: 752: 749: 740: 737: 712:Main article: 709: 706: 669: 666: 616: 613: 611: 608: 605:reprogramming. 594: 593: 575: 567: 551: 526: 523: 522: 521: 513: 504:: LIN28 is an 497: 489: 464: 439: 410: 344: 341: 331: 328: 302: 299: 297: 294: 269: 266: 241: 238: 234:reporter genes 175: 172: 26: 9: 6: 4: 3: 2: 6510: 6499: 6496: 6494: 6491: 6489: 6486: 6485: 6483: 6468: 6467: 6458: 6457: 6454: 6448: 6445: 6443: 6440: 6438: 6435: 6433: 6430: 6428: 6425: 6423: 6420: 6418: 6415: 6414: 6412: 6408: 6400: 6397: 6396: 6395: 6392: 6388: 6385: 6383: 6380: 6378: 6375: 6373: 6369: 6366: 6365: 6364: 6361: 6357: 6354: 6352: 6349: 6348: 6347: 6344: 6340: 6337: 6335: 6332: 6330: 6327: 6326: 6325: 6322: 6321: 6319: 6317: 6313: 6307: 6304: 6302: 6299: 6297: 6294: 6292: 6289: 6288: 6286: 6284:Sources/types 6282: 6278: 6271: 6266: 6264: 6259: 6257: 6252: 6251: 6248: 6242: 6238: 6235: 6232: 6230: 6227: 6225: 6221: 6218: 6215: 6213: 6210: 6207: 6204: 6202: 6198: 6195: 6192: 6190: 6187: 6185: 6182: 6180: 6177: 6176: 6163: 6159: 6154: 6149: 6145: 6141: 6137: 6133: 6129: 6125: 6121: 6114: 6106: 6102: 6095: 6089: 6087: 6082: 6075: 6071: 6066: 6061: 6056: 6051: 6047: 6043: 6039: 6032: 6030: 6014: 6010: 6003: 5995: 5991: 5986: 5981: 5976: 5971: 5967: 5963: 5959: 5952: 5936: 5932: 5928: 5922: 5906: 5902: 5896: 5881: 5880: 5875: 5868: 5866: 5849: 5845: 5841: 5834: 5826: 5822: 5817: 5812: 5807: 5802: 5798: 5794: 5790: 5783: 5775: 5771: 5767: 5763: 5759: 5755: 5751: 5747: 5740: 5724: 5718: 5710: 5706: 5701: 5696: 5692: 5688: 5684: 5677: 5661: 5657: 5651: 5635: 5631: 5625: 5609: 5605: 5599: 5591: 5587: 5582: 5577: 5573: 5569: 5565: 5561: 5557: 5553: 5549: 5541: 5533: 5529: 5524: 5519: 5515: 5511: 5507: 5503: 5499: 5492: 5484: 5480: 5476: 5472: 5468: 5464: 5460: 5456: 5452: 5448: 5441: 5433: 5429: 5424: 5419: 5415: 5411: 5407: 5403: 5399: 5395: 5391: 5384: 5376: 5372: 5367: 5362: 5358: 5354: 5350: 5346: 5342: 5335: 5327: 5323: 5318: 5313: 5309: 5305: 5301: 5297: 5294:(3): 107925. 5293: 5289: 5285: 5277: 5269: 5265: 5260: 5255: 5251: 5247: 5244:(8): 855–60. 5243: 5239: 5235: 5228: 5220: 5216: 5211: 5206: 5202: 5198: 5195:(5): 435–42. 5194: 5190: 5186: 5179: 5171: 5167: 5162: 5157: 5153: 5149: 5146:(3): 359–72. 5145: 5141: 5137: 5130: 5114: 5107: 5099: 5095: 5091: 5087: 5083: 5079: 5075: 5071: 5067: 5063: 5056: 5048: 5044: 5040: 5036: 5032: 5028: 5024: 5020: 5016: 5012: 5005: 4990: 4986: 4982: 4978: 4974: 4970: 4963: 4955: 4951: 4946: 4941: 4937: 4933: 4929: 4925: 4921: 4913: 4905: 4901: 4896: 4891: 4887: 4883: 4878: 4873: 4869: 4865: 4861: 4854: 4846: 4842: 4837: 4832: 4828: 4824: 4820: 4816: 4812: 4808: 4804: 4796: 4788: 4784: 4779: 4774: 4770: 4766: 4762: 4758: 4754: 4747: 4739: 4735: 4730: 4725: 4721: 4717: 4714:(4): 582–96. 4713: 4709: 4705: 4698: 4682: 4675: 4667: 4663: 4658: 4653: 4649: 4645: 4642:(2): 115–30. 4641: 4637: 4633: 4626: 4618: 4614: 4610: 4606: 4602: 4598: 4594: 4590: 4583: 4575: 4571: 4566: 4561: 4556: 4551: 4547: 4543: 4539: 4532: 4524: 4520: 4515: 4510: 4506: 4502: 4498: 4494: 4490: 4483: 4475: 4471: 4466: 4461: 4457: 4453: 4450:(5): 877–86. 4449: 4445: 4441: 4434: 4426: 4422: 4417: 4412: 4407: 4402: 4398: 4394: 4391:(6): 2152–6. 4390: 4386: 4382: 4375: 4367: 4363: 4359: 4355: 4351: 4347: 4343: 4339: 4335: 4331: 4323: 4315: 4311: 4307: 4303: 4299: 4295: 4290: 4285: 4281: 4277: 4270: 4262: 4258: 4253: 4248: 4244: 4240: 4236: 4232: 4228: 4221: 4213: 4209: 4205: 4201: 4196: 4191: 4187: 4183: 4179: 4175: 4171: 4167: 4160: 4152: 4148: 4143: 4138: 4134: 4130: 4127:(3): 360–73. 4126: 4122: 4118: 4111: 4103: 4099: 4094: 4089: 4084: 4079: 4075: 4071: 4067: 4063: 4059: 4052: 4044: 4040: 4035: 4030: 4026: 4022: 4019:(5): 1050–6. 4018: 4014: 4010: 4003: 3995: 3991: 3986: 3981: 3977: 3973: 3969: 3965: 3961: 3957: 3953: 3946: 3938: 3934: 3930: 3926: 3922: 3918: 3914: 3910: 3906: 3902: 3895: 3893: 3884: 3880: 3875: 3870: 3866: 3862: 3858: 3851: 3843: 3839: 3834: 3829: 3825: 3821: 3818:(2): 249–57. 3817: 3813: 3809: 3802: 3794: 3790: 3785: 3780: 3776: 3772: 3769:(5): 459–61. 3768: 3764: 3760: 3753: 3745: 3741: 3737: 3733: 3730:(2): 208–14. 3729: 3725: 3718: 3716: 3714: 3697: 3690: 3675: 3671: 3664: 3658: 3652: 3646: 3640: 3632: 3628: 3624: 3620: 3615: 3610: 3606: 3602: 3598: 3591: 3583: 3579: 3574: 3569: 3564: 3559: 3555: 3551: 3547: 3540: 3538: 3529: 3525: 3520: 3515: 3511: 3507: 3504:(11): 805–8. 3503: 3499: 3495: 3488: 3472: 3471:Science Daily 3468: 3462: 3454: 3450: 3446: 3442: 3438: 3434: 3430: 3426: 3422: 3418: 3411: 3396: 3392: 3388: 3384: 3380: 3376: 3369: 3361: 3357: 3352: 3347: 3344:(5): 568–74. 3343: 3339: 3335: 3328: 3326: 3317: 3313: 3308: 3303: 3299: 3295: 3291: 3287: 3283: 3276: 3268: 3264: 3260: 3256: 3252: 3248: 3244: 3240: 3236: 3232: 3225: 3223: 3214: 3210: 3205: 3200: 3196: 3192: 3188: 3184: 3180: 3176: 3172: 3165: 3150: 3146: 3139: 3131: 3127: 3120: 3112: 3108: 3103: 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2330: 2325: 2320: 2316: 2312: 2308: 2304: 2300: 2293: 2285: 2281: 2276: 2271: 2267: 2263: 2259: 2252: 2250: 2241: 2237: 2232: 2227: 2223: 2219: 2215: 2208: 2206: 2204: 2195: 2191: 2187: 2183: 2179: 2175: 2171: 2167: 2163: 2159: 2152: 2150: 2141: 2137: 2132: 2127: 2122: 2117: 2114:(5): 861–72. 2113: 2109: 2105: 2098: 2082: 2078: 2072: 2064: 2060: 2055: 2050: 2046: 2042: 2038: 2031: 2023: 2019: 2015: 2011: 2007: 2003: 1999: 1995: 1991: 1987: 1980: 1972: 1968: 1964: 1960: 1956: 1952: 1948: 1944: 1940: 1936: 1929: 1921: 1917: 1912: 1907: 1903: 1899: 1895: 1891: 1887: 1883: 1879: 1871: 1863: 1859: 1854: 1849: 1845: 1841: 1838:(4): 818–25. 1837: 1833: 1829: 1822: 1814: 1810: 1806: 1802: 1798: 1794: 1787: 1779: 1775: 1770: 1765: 1760: 1755: 1752:(1): hoy024. 1751: 1747: 1743: 1736: 1720: 1716: 1710: 1694: 1690: 1684: 1668: 1664: 1660: 1654: 1647: 1646:Yamanaka 2010 1642: 1634: 1630: 1625: 1620: 1616: 1612: 1609:(5): 573–86. 1608: 1604: 1600: 1593: 1585: 1581: 1577: 1573: 1569: 1565: 1561: 1557: 1553: 1549: 1542: 1534: 1530: 1525: 1520: 1515: 1510: 1506: 1502: 1498: 1491: 1483: 1477: 1469: 1462: 1458: 1453: 1448: 1443: 1438: 1435:(4): 663–76. 1434: 1430: 1426: 1419: 1417: 1415: 1413: 1408: 1398: 1395: 1393: 1390: 1388: 1385: 1383: 1380: 1377: 1374: 1372: 1369: 1367: 1364: 1363: 1357: 1355: 1344: 1342: 1338: 1334: 1330: 1326: 1322: 1318: 1314: 1310: 1306: 1302: 1298: 1288: 1284: 1282: 1277: 1272: 1270: 1266: 1262: 1258: 1254: 1250: 1246: 1242: 1238: 1228: 1225: 1221: 1217: 1214: 1203: 1200: 1197: 1193: 1189: 1187: 1183: 1179: 1169: 1167: 1162: 1160: 1156: 1152: 1148: 1144: 1137:Tissue repair 1134: 1132: 1128: 1127:reprogramming 1118: 1116: 1112: 1107: 1103: 1099: 1095: 1091: 1087: 1086:blood vessels 1083: 1079: 1075: 1071: 1061: 1059: 1048: 1046: 1040: 1027: 1023: 1018: 1014: 1010: 1006: 1002: 999: 995: 994: 982: 978: 975: 971: 967: 963: 959: 955: 951: 950: 948: 943: 940: 937: 933: 929: 925: 921: 917: 914: 910: 907: 903: 899: 896: 892: 888: 884: 881: 877: 874: 870: 869:catecholamine 866: 862: 861: 859: 854: 850: 846: 842: 839: 835: 832: 828: 825: 821: 817: 816: 814: 813: 812: 809: 805: 800: 798: 794: 790: 789:embryoid body 786: 778: 774: 770: 766: 762: 757: 748: 745: 739:RNA molecules 736: 734: 730: 724: 722: 715: 705: 703: 699: 695: 691: 685: 681: 679: 675: 665: 663: 659: 653: 651: 647: 643: 638: 635: 631: 627: 622: 602: 598: 591: 588: 584: 580: 576: 573: 568: 565: 561: 557: 552: 549: 545: 541: 536: 532: 531: 530: 519: 518: 514: 511: 507: 503: 502: 498: 495: 494: 490: 487: 483: 479: 474: 470: 469: 465: 462: 458: 454: 449: 445: 444: 440: 436: 432: 428: 424: 420: 416: 415: 411: 408: 404: 400: 395: 391: 387: 383: 382: 378: 377: 376: 374: 370: 366: 362: 358: 354: 350: 347: 340: 336: 327: 325: 321: 316: 312: 311:James Thomson 308: 293: 291: 285: 283: 279: 275: 265: 261: 259: 255: 251: 247: 237: 235: 229: 227: 223: 219: 215: 211: 202: 198: 194: 190: 186: 181: 180:Reprogramming 171: 169: 165: 160: 158: 153: 150: 144: 142: 138: 134: 129: 127: 122: 120: 116: 112: 108: 104: 100: 96: 92: 88: 84: 80: 77: 73: 69: 65: 57: 50: 46: 42: 38: 34: 30: 19: 6464: 6393: 6362: 6345: 6323: 6316:Cell potency 6305: 6127: 6123: 6113: 6104: 6094: 6078: 6045: 6041: 6016:. Retrieved 6012: 6002: 5965: 5961: 5951: 5939:. Retrieved 5935:the original 5930: 5921: 5909:. Retrieved 5905:the original 5895: 5883:. Retrieved 5877: 5852:. Retrieved 5848:the original 5843: 5833: 5796: 5792: 5782: 5752:(9): 890–1. 5749: 5745: 5739: 5727:. Retrieved 5717: 5690: 5686: 5676: 5664:. Retrieved 5659: 5650: 5638:. Retrieved 5633: 5624: 5612:. Retrieved 5607: 5598: 5555: 5551: 5540: 5505: 5501: 5491: 5450: 5446: 5440: 5397: 5393: 5383: 5351:(4): 360–4. 5348: 5344: 5334: 5291: 5288:Cell Reports 5287: 5276: 5241: 5237: 5227: 5192: 5188: 5178: 5143: 5139: 5129: 5117:. Retrieved 5106: 5065: 5061: 5055: 5014: 5010: 5004: 4992:. Retrieved 4972: 4962: 4927: 4923: 4912: 4867: 4863: 4853: 4810: 4806: 4795: 4760: 4756: 4746: 4711: 4707: 4697: 4685:. 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