Suppression of induced pluripotent stem cell generation by the p53–p21 pathway
Open accessAbstract
Induced pluripotent stem (iPS) cells can be generated from somatic cells by the introduction of Oct3/4 (also known as Pou5f1), Sox2, Klf4 and c-Myc, in mouse and in human. The efficiency of this process, however, is low. Pluripotency can be induced without c-Myc, but with even lower efficiency. A p53 (also known as TP53 in humans and Trp53 in mice) short-interfering RNA (siRNA) was recently shown to promote human iPS cell generation, but the specificity and mechanisms remain to be determined. Here we report that up to 10% of transduced mouse embryonic fibroblasts lacking p53 became iPS cells, even without the Myc retrovirus. The p53 deletion also promoted the induction of integration-free mouse iPS cells with plasmid transfection. Furthermore, in the p53-null background, iPS cells were generated from terminally differentiated T lymphocytes. The suppression of p53 also increased the efficiency of human iPS cell generation. DNA microarray analyses identified 34 p53-regulated genes that are common in mouse and human fibroblasts. Functional analyses of these genes demonstrate that the p53-p21 pathway serves as a barrier not only in tumorigenicity, but also in iPS cell generation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
OSKM induction activates the p53-p21 pathway.
“It is known that OSKM induction activates the p53–p21 pathway25.”
From In vivo partial reprogramming of myofibers promotes muscle regeneration by remodeling the stem cell niche (2021) · cites this paper as [25]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Takahashi, K., & Yamanaka, S. (2006) · Cell · doi:10.1016/j.cell.2006.07.024 · Cited by 26,673 · see citing works
Self-citationInduction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007) · Cell · doi:10.1016/j.cell.2007.11.019 · Cited by 20,221 · see citing works
Self-citationInduced Pluripotent Stem Cell Lines Derived from Human Somatic Cells
Yu, J., Vodyanik, M. A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J. L., Tian, S., Nie, J., Jonsdottir, G. A., Ruotti, V., Stewart, R., et al. (2007) · Science · doi:10.1126/science.1151526 · Cited by 10,310 · see citing works
Generation of germline-competent induced pluripotent stem cells
Okita, K., Ichisaka, T., & Yamanaka, S. (2007) · Nature · doi:10.1038/nature05934 · Cited by 4,438 · see citing works
Self-citationReprogramming of human somatic cells to pluripotency with defined factors
Park, I.-H., Zhao, R., West, J. A., Yabuuchi, A., Huo, H.-G., Ince, T., Lerou, P., Lensch, M., & Daley, G. Q. (2008) · Nature · doi:10.1038/nature06534 · Cited by 3,028 · see citing works
Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts
Nakagawa, M., Koyanagi, M., Tanabe, K., Takahashi, K., Ichisaka, T., Aoi, T., Okita, K., Mochiduki, Y., Takizawa, N., & Yamanaka, S. (2007) · Nature Biotechnology · doi:10.1038/nbt1374 · Cited by 2,781 · see citing works
Self-citationIn vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state
Wernig, M., Meissner, A., Foreman, R. K., Brambrink, T., Ku, M., Hochedlinger, K., Bernstein, B., & Jaenisch, R. (2007) · Nature · doi:10.1038/nature05944 · Cited by 2,654 · see citing works
Generation of Mouse Induced Pluripotent Stem Cells Without Viral Vectors
Okita, K., Nakagawa, M., Hong, H., Ichisaka, T., & Yamanaka, S. (2008) · Science · doi:10.1126/science.1164270 · Cited by 2,002 · see citing works
Self-citationMaherali, N., Sridharan, R., Xie, W., Utikal, J., Eminli, S., Arnold, K., Stadtfeld, M., Yachechko, R., Tchieu, J., Jaenisch, R., et al. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.05.014 · Cited by 1,725 · see citing works
Plat-E: an efficient and stable system for transient packaging of retroviruses
MORITA, S., Kojima, T., & Kitamura, T. (2000) · Gene Therapy · doi:10.1038/sj.gt.3301206 · Cited by 1,660 · see citing works
Lentivirus-delivered stable gene silencing by RNAi in primary cells.
Stewart, S. A., Dykxhoorn, D. M., Palliser, D., Mizuno, H., Yu, E. Y., An, D., Sabatini, D., Chen, I. S. Y., Hahn, W., Sharp, P., et al. (2003) · RNA: A publication of the RNA Society · doi:10.1261/rna.2192803 · Cited by 1,619 · see citing works
Generation of Pluripotent Stem Cells from Adult Mouse Liver and Stomach Cells
Aoi, T., Yae, K., Nakagawa, M., Ichisaka, T., Okita, K., Takahashi, K., Chiba, T., & Yamanaka, S. (2008) · Science · doi:10.1126/science.1154884 · Cited by 1,079 · see citing works
Self-citationGeneration of human induced pluripotent stem cells from dermal fibroblasts
Lowry, W. E., Richter, L., Yachechko, R., Pyle, A. D., Tchieu, J., Sridharan, R., Clark, A. T., & Plath, K. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711983105 · Cited by 1,041 · see citing works
Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells
Tada, M., Takahama, Y., Abe, K., Nakatsuji, N., & Tada, T. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00459-6 · Cited by 891 · see citing works
Strategies and New Developments in the Generation of Patient-Specific Pluripotent Stem Cells
Yamanaka, S. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.05.012 · Cited by 737 · see citing works
Self-citationYamanaka, S. (2009) · Cell · doi:10.1016/j.cell.2009.03.034 · Cited by 659 · see citing works
Self-citationc-Myc Is Dispensable for Direct Reprogramming of Mouse Fibroblasts
Wernig, M., Meissner, A., Cassady, J. P., & Jaenisch, R. (2008) · Cell stem cell · doi:10.1016/j.stem.2007.12.001 · Cited by 627 · see citing works
Elite and stochastic models for induced pluripotent stem cell generation
Yamanaka, S. (2009) · Nature · doi:10.1038/nature08180 · Cited by 551 · see citing works
Self-citationTwo Supporting Factors Greatly Improve the Efficiency of Human iPSC Generation
Zhao, Y., Yin, X., Qin, H., Zhu, F., Liu, H., Yang, W., Zhang, Q., Xiang, C., Hou, P., Song, Z., et al. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2008.10.002 · Cited by 468 · see citing works
Targeted point mutations of p53 lead to dominant-negative inhibition of wild-type p53 function
de Vries, A., Flores, E. R., Miranda, B., Hsieh, H.-M., van Oostrom, C. T. M., Sage, J., & Jacks, T. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.052713099 · Cited by 207 · see citing works
Shinmura, K., Bennett, R. A. O., Tarapore, P., & Fukasawa, K. (2006) · Oncogene · doi:10.1038/sj.onc.1210085 · Cited by 87 · see citing works
Tissue-specific inactivation of p53 tumor suppression in the mouse.Preprint
Bowman, T., Symonds, H., Gu, L., Yin, C., Oren, M., & Dyke, T. V. (1996) · Genes & Development · doi:10.1101/gad.10.7.826 · Cited by 80 · see citing works
Ser58 of mouse p53 is the homologue of human Ser46 and is phosphorylated by HIPK2 in apoptosis
Cecchinelli, B., Porrello, A., Lazzari, C., Gradi, A., Bossi, G., D'Angelo, M., Sacchi, A., & Soddu, S. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401933 · Cited by 31 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors
Ieda, M., Fu, J.-D., Delgado-Olguin, P., Vedantham, V., Hayashi, Y., Bruneau, B. G., & Srivastava, D. (2010) · Cell · doi:10.1016/j.cell.2010.07.002 · Cited by 2,454 · see citing works
A more efficient method to generate integration-free human iPS cells
Okita, K., Matsumura, Y., Sato, Y., Okada, A., Morizane, A., Okamoto, S., Hong, H., Nakagawa, M., Tanabe, K., Tezuka, K.-I., et al. (2011) · Nature Methods · doi:10.1038/nmeth.1591 · Cited by 2,061 · see citing works
Self-citationThe essence of senescence: Figure 1.
Kuilman, T., Michaloglou, C., Mooi, W. J., & Peeper, D. S. (2010) · Genes & Development · doi:10.1101/gad.1971610 · Cited by 2,038 · see citing works
The Cancer Stem Cell Niche: How Essential Is the Niche in Regulating Stemness of Tumor Cells?
Plaks, V., Kong, N., & Werb, Z. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2015.02.015 · Cited by 1,557 · see citing works
Emerging trends in regenerative medicine: a scientometric analysis inCiteSpace
Chen, C., Hu, Z., Liu, S., & Tseng, H. (2012) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2012.674507 · Cited by 1,391 · see citing works
Unravelling mechanisms of p53-mediated tumour suppression
Bieging-Rolett, K. T., Mello, S. S., & Attardi, L. D. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3711 · Cited by 1,389 · see citing works
Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury
Yang, L., Besschetnova, T. Y., Brooks, C. R., Shah, J. V., & Bonventre, J. V. (2010) · Nature Medicine · doi:10.1038/nm.2144 · Cited by 1,333 · see citing works
Somatic coding mutations in human induced pluripotent stem cells
Gore, A., Li, Z., Fung, H.-L., Young, J. E., Agarwal, S., Antosiewicz-Bourget, J., Canto, I., Giorgetti, A., Israel, M. A., Kiskinis, E., et al. (2011) · Nature · doi:10.1038/nature09805 · Cited by 1,273 · see citing works
Cellular Senescence: Aging, Cancer, and Injury
Calcinotto, A., Kohli, J., Zagato, E., Pellegrini, L., Demaria, M., & Alimonti, A. (2019) · Physiological Reviews · doi:10.1152/physrev.00020.2018 · Cited by 1,270 · see citing works
Pluripotent Stem Cell-Based Cell Therapy—Promise and Challenges
Yamanaka, S. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.09.014 · Cited by 1,230 · see citing works
Self-citationKu, S., Rosario, S. R., Wang, Y., Mu, P., Seshadri, M., Goodrich, Z., Goodrich, M. M., Labbé, D. P., Gomez, E. C., Wang, J., et al. (2017) · Science · doi:10.1126/science.aah4199 · Cited by 1,093 · see citing works
P53 in survival, death and metabolic health: a lifeguard with a licence to kill.
Kruiswijk, F., Labuschagne, C. F., & Vousden, K. H. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm4007 · Cited by 1,080 · see citing works
Mu, P., Zhang, Z., Benelli, M., Karthaus, W. R., Hoover, E., Chen, C.-C., Wongvipat, J., Ku, S., Gao, D., Cao, Z., et al. (2017) · Science · doi:10.1126/science.aah4307 · Cited by 1,063 · see citing works
Rivlin, N., Brosh, R., Oren, M., & Rotter, V. (2011) · Genes & Cancer · doi:10.1177/1947601911408889 · Cited by 1,033 · see citing works
Oncogenic roles of EMT-inducing transcription factors
Puisieux, A., Brabletz, T., & Caramel, J. (2014) · Nature Cell Biology · doi:10.1038/ncb2976 · Cited by 1,032 · see citing works
Direct cell reprogramming is a stochastic process amenable to acceleration
Hanna, J. H., Saha, K., Pando, B., van Zon, J. S., Lengner, C. J., Creyghton, M. P., van Oudenaarden, A., & Jaenisch, R. (2009) · Nature · doi:10.1038/nature08592 · Cited by 1,006 · see citing works
p53 inhibits CRISPR–Cas9 engineering in human pluripotent stem cells
Ihry, R. J., Worringer, K. A., Salick, M. R., Frias, E., Ho, D., Theriault, K., Kommineni, S., Chen, J., Sondey, M., Ye, C., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0050-6 · Cited by 978 · see citing works
Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells
Loewer, S., Cabili, M. N., Guttman, M., Loh, Y., Thomas, K., Park, I. H., Garber, M. G., Curran, M. S., Önder, T. T., Agarwal, S., et al. (2010) · Nature Genetics · doi:10.1038/ng.710 · Cited by 971 · see citing works
Vitamin C enhances the generation of mouse and human induced pluripotent stem cells.
Esteban, M., Wang, T., Qin, B.-M., Yang, J.-Y., Qin, D.-J., Cai, J.-L., Li, W., Weng, Z., Chen, J.-K., Ni, S., et al. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2009.12.001 · Cited by 989 · see citing works
Copy number variation and selection during reprogramming to pluripotency
Hussein, S. M. I., Batada, N., Vuoristo, S., Ching, R., Autio, R., Närvä, E., Ng, S., Sourour, M., Hämäläinen, R., Olsson, C., et al. (2011) · Nature · doi:10.1038/nature09871 · Cited by 992 · see citing works
The tumorigenicity of human embryonic and induced pluripotent stem cells
Ben-David, U., & Benvenisty, N. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3034 · Cited by 889 · see citing works
Soufi, A., Donahue, G., & Zaret, K. (2012) · Cell · doi:10.1016/j.cell.2012.09.045 · Cited by 888 · see citing works
A decade of transcription factor-mediated reprogramming to pluripotency
Takahashi, K., & Yamanaka, S. (2016) · Nature reviews. Molecular cell biology · doi:10.1038/nrm.2016.8 · Cited by 815 · see citing works
Self-citationEmerging trends and new developments in regenerative medicine: a scientometric update (2000 – 2014)
Chen, C., Dubin, R., & Kim, M. C. (2014) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2014.920813 · Cited by 857 · see citing works
Cellular senescence and its effector programs
Salama, R., Sadaie, M., Hoare, M., & Narita, M. (2014) · Genes & Development · doi:10.1101/gad.235184.113 · Cited by 855 · see citing works
Induced pluripotency: history, mechanisms, and applicationsPreprint
Stadtfeld, M., & Hochedlinger, K. (2010) · Genes & Development · doi:10.1101/gad.1963910 · Cited by 827 · see citing works
A Small-Molecule Inhibitor of Tgf-β Signaling Replaces Sox2 in Reprogramming by Inducing Nanog
Ichida, J. K., Blanchard, J., Lam, K., Son, E. Y., Chung, J. E., Egli, D., Loh, K. M., Carter, A. C., Di Giorgio, F. P., Koszka, K., et al. (2009) · Cell Stem Cell · doi:10.1016/j.stem.2009.09.012 · Cited by 808 · see citing works
Buganim, Y., Faddah, D. A., Cheng, A. W., Itskovich, E., Markoulaki, S., Ganz, K., Klemm, S. L., van Oudenaarden, A., & Jaenisch, R. (2012) · Cell · doi:10.1016/j.cell.2012.08.023 · Cited by 800 · see citing works
Nuclear reprogramming to a pluripotent state by three approaches
Yamanaka, S., & Blau, H. (2010) · Nature · doi:10.1038/nature09229 · Cited by 799 · see citing works
Self-citationTumor suppressor p53: Biology, signaling pathways, and therapeutic targeting
Borrero, L. J. H., & El‐Deiry, W. S. (2021) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2021.188556 · Cited by 773 · see citing works
The role of YAP transcription coactivator in regulating stem cell self-renewal and differentiationPreprint
Lian, I., Kim, J., Okazawa, H., Zhao, J. J., Zhao, B., Yu, J., Chinnaiyan, A. M., Israel, M. A., Goldstein, L. S. B., Abujarour, R., et al. (2010) · Genes & Development · doi:10.1101/gad.1903310 · Cited by 738 · see citing works
Prigione, A., Fauler, B., Lurz, R., Lehrach, H., & Adjaye, J. (2010) · Stem Cells · doi:10.1002/stem.404 · Cited by 617 · see citing works
Subramanyam, D., Lamouille, S., Judson, R. L., Liu, J. Y., Bucay, N., Derynck, R., & Blelloch, R. H. (2011) · Nature Biotechnology · doi:10.1038/nbt.1862 · Cited by 594 · see citing works
Tissue damage and senescence provide critical signals for cellular reprogramming in vivo
Mosteiro, L., Pantoja, C., Alcazar, N., Marión, R. M., Chondronasiou, D., Rovira, M., Fernandez-Marcos, P. J., Muñoz-Martin, M., Blanco-Aparicio, C., Pastor, J., et al. (2016) · Science · doi:10.1126/science.aaf4445 · Cited by 589 · see citing works
Seki, T., Yuasa, S., Oda, M., Egashira, T., Yae, K., Kusumoto, D., Nakata, H., Tohyama, S., Hashimoto, H., Kodaira, M., et al. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.06.003 · Cited by 584 · see citing works
The dynamic nature of senescence in cancer
Lee, S., & Schmitt, C. A. (2019) · Nature Cell Biology · doi:10.1038/s41556-018-0249-2 · Cited by 588 · see citing works
Advances in Pluripotent Stem Cells: History, Mechanisms, Technologies, and Applications
Liu, G., David, B. T., Trawczynski, M., & Fessler, R. G. (2019) · Stem Cell Reviews and Reports · doi:10.1007/s12015-019-09935-x · Cited by 527 · see citing works
Cancer stem cells in the development of liver cancer
Yamashita, T., & Wang, X. W. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66024 · Cited by 526 · see citing works
Sox2 expression in breast tumours and activation in breast cancer stem cells
Leis, O., Eguiara, A., López‐Arribillaga, E., Alberdi, M. J., Hernández-García, S., Elorriaga, K., Pandiella, A., Rezola, R., & Martín, Á. G. (2011) · Oncogene · doi:10.1038/onc.2011.338 · Cited by 518 · see citing works
Methods for making induced pluripotent stem cells: reprogramming à la carte
Gonzãlez, F., Boué, S., & Belmonte, J. C. I. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2937 · Cited by 504 · see citing works
Ohnishi, K., Semi, K., Yamamoto, T., Shimizu, M., Tanaka, A., Mitsunaga, K., Okita, K., Osafune, K., Arioka, Y., Maeda, T., et al. (2014) · Cell · doi:10.1016/j.cell.2014.01.005 · Cited by 460 · see citing works
Self-citationReprogramming of peripheral blood cells to induced pluripotent stem cells
Staerk, J., Dawlaty, M., Gao, Q., Maetzel, D., Hanna, J., Sommer, C., Mostoslavsky, G., & Jaenisch, R. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.06.002 · Cited by 418 · see citing works
CHK2 kinase in the DNA damage response and beyond
Zannini, L., Delia, D., & Buscemi, G. (2014) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mju045 · Cited by 455 · see citing works
NANOG-dependent function of TET1 and TET2 in establishment of pluripotency
Costa, Y., Ding, J., Theunissen, T. W., Faiola, F., Hore, T. A., Shliaha, P. V., Fidalgo, M., Saunders, A., Lawrence, M., Dietmann, S., et al. (2013) · Nature · doi:10.1038/nature11925 · Cited by 433 · see citing works
Examination of the expanding pathways for the regulation of p21 expression and activity
Jung, Y.-S., Qian, Y., & Chen, X. (2010) · Cellular Signalling · doi:10.1016/j.cellsig.2010.01.013 · Cited by 418 · see citing works
Primordial Germ Cells in MicePreprint
Saitou, M., & Yamaji, M. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008375 · Cited by 418 · see citing works
Steps Toward Safe Cell Therapy Using Induced Pluripotent Stem Cells
Okano, H., Nakamura, M., Yoshida, K., Okada, Y., Tsuji, O., Nori, S., Ikeda, E., Yamanaka, S., & Miura, K. (2013) · Circulation Research · doi:10.1161/circresaha.111.256149 · Cited by 413 · see citing works
Self-citationThe cell cycle in stem cell proliferation, pluripotency and differentiation
Liu, L., Michowski, W., Kołodziejczyk, A., & Siciński, P. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0384-4 · Cited by 404 · see citing works
Promotion of direct reprogramming by transformation-deficient Myc
Nakagawa, M., Takizawa, N., Narita, M., Ichisaka, T., & Yamanaka, S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009374107 · Cited by 403 · see citing works
Self-citationSystemic Elevation of PTEN Induces a Tumor-Suppressive Metabolic State
Garcı́a-Cao, I., Song, M. S., Hobbs, R. M., Laurent, G., Giorgi, C., de Boer, V. C. J., Anastasiou, D., Ito, K., Sasaki, A. T., Rameh, L. E., et al. (2012) · Cell · doi:10.1016/j.cell.2012.02.030 · Cited by 403 · see citing works
Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1
Maekawa, M., Yamaguchi, K., Nakamura, T., Shibukawa, R., Kodanaka, I., Ichisaka, T., Kawamura, Y., Mochizuki, H., Goshima, N., & Yamanaka, S. (2011) · Nature · doi:10.1038/nature10106 · Cited by 388 · see citing works
Self-citationmiR-34 miRNAs provide a barrier for somatic cell reprogramming
Choi, Y. J., Lin, C., Ho, J. J., He, X., Okada, N., Bu, P., Zhong, Y., Kim, S. Y., Bennett, M. J., Chen, C., et al. (2011) · Nature Cell Biology · doi:10.1038/ncb2366 · Cited by 381 · see citing works
Feng, Q., Lu, S., Klimanskaya, I. V., Gomes, I., Kim, D., Chung, Y., Honig, G. R., Kim, K., & Lanza, R. (2010) · Stem Cells · doi:10.1002/stem.321 · Cited by 371 · see citing works
Induced Pluripotent Stem Cells and Their Use in Human Models of Disease and Development.
Karagiannis, P., Takahashi, K., Saito, M., Yoshida, Y., Okita, K., Watanabe, A., Inoue, H., Yamashita, J. K., Todani, M., Nakagawa, M., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00039.2017 · Cited by 313 · see citing works
Self-citationThe regulation of energy metabolism and the IGF-1/mTOR pathways by the p53 protein
Feng, Z., & Levine, A. J. (2010) · Trends in Cell Biology · doi:10.1016/j.tcb.2010.03.004 · Cited by 359 · see citing works
Mesenchymal–endothelial transition contributes to cardiac neovascularization
Ubil, E., Duan, J., Pillai, I. C. L., Rosa‐Garrido, M., Wu, Y., Bargiacchi, F., Lu, Y., Stanbouly, S., Huang, J., Rojas, M., et al. (2014) · Nature · doi:10.1038/nature13839 · Cited by 358 · see citing works
SOX2 promotes dedifferentiation and imparts stem cell-like features to pancreatic cancer cells
Herreros‐Villanueva, M., Js, Z., König, A. O., Abel, E. V., Smyrk, T. C., Bamlet, W. R., de Narvajas, A. A.-M., Gomez, T. S., Simeone, D. M., Bujanda, L., et al. (2013) · Oncogenesis · doi:10.1038/oncsis.2013.23 · Cited by 326 · see citing works
Reprogramming of T Cells from Human Peripheral Blood
Loh, Y., Hartung, O., Li, H., Guo, C., Sahalie, J. M., Manos, P. D., Urbach, A., Heffner, G. C., Grs̆ković, M., Vigneault, F., et al. (2010) · Cell stem cell · doi:10.1016/j.stem.2010.06.004 · Cited by 320 · see citing works
Ruiz, S., Panopoulos, A. D., Herrerías, A., Bissig, K., Lutz, M. K., Berggren, W. T., Verma, I., & Belmonte, J. C. I. (2010) · Current Biology · doi:10.1016/j.cub.2010.11.049 · Cited by 328 · see citing works
The Multifaceted p21 (Cip1/Waf1/CDKN1A) in Cell Differentiation, Migration and Cancer Therapy
Kreis, N., Louwen, F., & Yuan, J. (2019) · Cancers · doi:10.3390/cancers11091220 · Cited by 309 · see citing works
Small RNA‐mediated regulation of iPS cell generation
Li, Z., Yang, C., Nakashima, K., & Rana, T. M. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.2 · Cited by 301 · see citing works
Role of Sirtuin1-p53 regulatory axis in aging, cancer and cellular reprogramming
Ong, A. L. C., & Ramasamy, T. S. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.02.004 · Cited by 301 · see citing works
Bezzi, M., Teo, S. X., Müller, J., Mok, W. C., Sahu, S. K., Vardy, L. A., Bonday, Z., & Guccione, E. (2013) · Genes & Development · doi:10.1101/gad.219899.113 · Cited by 302 · see citing works
Cellular senescence in development, regeneration and disease
Rhinn, M., Ritschka, B., & Keyes, W. M. (2019) · Development · doi:10.1242/dev.151837 · Cited by 296 · see citing works
Redox homeostasis: the linchpin in stem cell self-renewal and differentiation
Wang, K., Zhang, T., Dong, Q. G., Nice, E. C., Huang, C., & Wei, Y. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.50 · Cited by 291 · see citing works
Progress in understanding reprogramming to the induced pluripotent state
Plath, K., & Lowry, W. (2011) · Nature reviews genetics · doi:10.1038/nrg2955 · Cited by 306 · see citing works
Defined factors induce reprogramming of gastrointestinal cancer cells
Miyoshi, N., Ishii, H., Nagai, K.-I., Hoshino, H., Mimori, K., Tanaka, F., Nagano, H., Sekimoto, M., Doki, Y., & Mori, M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912407107 · Cited by 280 · see citing works
The promises and perils of p53
Krizhanovsky, V., & Lowe, S. W. (2009) · Nature · doi:10.1038/4601085a · Cited by 274 · see citing works
Paull, D., Sevilla, A., Zhou, H., Hahn, A. K., Kim, H., Napolitano, C., Tsankov, A., Shang, L., Krumholz, K., Jagadeesan, P., et al. (2015) · Nature Methods · doi:10.1038/nmeth.3507 · Cited by 263 · see citing works
c-Met signaling induces a reprogramming network and supports the glioblastoma stem-like phenotype
Li, Y.-Q., Li, A., Glas, M., Lal, B., Ying, M., Sang, Y., Xia, S., Trageser, D., Guerrero‐Cazares, H., Eberhart, C. G., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016912108 · Cited by 266 · see citing works
Induced Pluripotent Stem Cells 10 Years Later
Yoshida, Y., & Yamanaka, S. (2017) · Circulation Research · doi:10.1161/circresaha.117.311080 · Cited by 266 · see citing works
Self-citationRETRACTED ARTICLE: Stimulus-triggered fate conversion of somatic cells into pluripotency
Obokata, H., Wakayama, T., Sasai, Y., Kojima, K., Vacanti, M. P., Niwa, H., Yamato, M., & Vacanti, C. A. (2014) · Nature · doi:10.1038/nature12968 · Cited by 259 · see citing works
RetractedInduced pluripotent stem cells: opportunities and challenges
Okita, K., & Yamanaka, S. (2011) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2011.0016 · Cited by 259 · see citing works
Self-citationDirect lineage conversions: unnatural but useful?
Vierbuchen, T., & Wernig, M. (2011) · Nature Biotechnology · doi:10.1038/nbt.1946 · Cited by 259 · see citing works
Warlich, E., Kuehle, J., Cantz, T., Brugman, M., Maetzig, T., Galla, M., Filipczyk, A., Halle, S., Klump, H., Schöler, H., et al. (2011) · Molecular Therapy · doi:10.1038/mt.2010.314 · Cited by 265 · see citing works
Ohnuki, M., Tanabe, K., Sutou, K., Teramoto, I., Sawamura, Y., Narita, M., Nakamura, M., Tokunaga, Y., Nakamura, M., Watanabe, A., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1413299111 · Cited by 256 · see citing works
Self-citationInduced Pluripotent Stem Cells: Problems and Advantages when Applying them in Regenerative Medicine
Medvedev, S. P., Shevchenko, A. I., & Zakian, S. M. (2010) · Acta Naturae · doi:10.32607/20758251-2010-2-2-18-27 · Cited by 232 · see citing works
p53-Dependent Nestin Regulation Links Tumor Suppression to Cellular Plasticity in Liver Cancer
Tschaharganeh, D. F., Xue, W., Calvisi, D. F., Evert, M., Michurina, T. V., Dow, L. E., Banito, A., Katz, S. F., Kastenhuber, E. R., Weissmueller, S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.05.051 · Cited by 227 · see citing works
Deconstructing networks of p53-mediated tumor suppression in vivo
Kaiser, A. M., & Attardi, L. D. (2017) · Cell Death and Differentiation · doi:10.1038/cdd.2017.171 · Cited by 227 · see citing works
p53 Regulates Cell Cycle and MicroRNAs to Promote Differentiation of Human Embryonic Stem Cells
Jain, A. K., Allton, K. L., Iacovino, M., Mahen, E. M., Milczarek, R. J., Zwaka, T. P., Kyba, M., & Barton, M. C. (2012) · PLoS Biology · doi:10.1371/journal.pbio.1001268 · Cited by 226 · see citing works
Pluripotent Stem Cells: Current Understanding and Future Directions
Romito, A., & Cobellis, G. (2015) · Stem Cells International · doi:10.1155/2016/9451492 · Cited by 224 · see citing works
Embryonic stem cell and induced pluripotent stem cell: an epigenetic perspective
Liang, G., & Zhang, Y. (2012) · Cell Research · doi:10.1038/cr.2012.175 · Cited by 223 · see citing works
Adenanthin targets peroxiredoxin I and II to induce differentiation of leukemic cells
Liu, C., Yin, Q., Zhou, H., Wu, Y., Pu, J., Li, X., Liu, W., Huang, X. Y., Jiang, T., Wu, M., et al. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.935 · Cited by 222 · see citing works
DNA methylation and cellular reprogramming
Carvalho, D. D. D., You, J. S., & Jones, P. A. (2010) · Trends in Cell Biology · doi:10.1016/j.tcb.2010.08.003 · Cited by 219 · see citing works
Generation of mouse-induced pluripotent stem cells with plasmid vectors
Okita, K., Hong, H., Takahashi, K., & Yamanaka, S. (2010) · Nature Protocols · doi:10.1038/nprot.2009.231 · Cited by 242 · see citing works
Self-citationHedgehog controls neural stem cells through p53‐independent regulation of Nanog
Pò, A., Ferretti, E., Miele, E., Smaele, E. D., Paganelli, A., Canettieri, G., Coni, S., Marcotullio, L. D., Biffoni, M., Massimi, L., et al. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.131 · Cited by 215 · see citing works
Different Facets of Aging in Human Mesenchymal Stem Cells
Wagner, W., Ho, A. D., & Zenke, M. (2010) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2009.0825 · Cited by 215 · see citing works
Lack of p21 expression links cell cycle control and appendage regeneration in mice
Bedelbaeva, K., Snyder, A., Gourevitch, D., Clark, L., Zhang, X.-M., Leferovich, J., Cheverud, J. M., Lieberman, P., & Heber-Katz, E. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000830107 · Cited by 207 · see citing works
Omole, A. E., & Fakoya, A. O. J. (2018) · PeerJ · doi:10.7717/peerj.4370 · Cited by 207 · see citing works
Dynamic single-cell imaging of direct reprogramming reveals an early specifying event
Smith, Z. D., Nachman, I., Regev, A., & Meissner, A. (2010) · Nature Biotechnology · doi:10.1038/nbt.1632 · Cited by 205 · see citing works
Deciphering p53 signaling in tumor suppression
Mello, S. S., & Attardi, L. D. (2017) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2017.11.005 · Cited by 203 · see citing works
Dedifferentiation and Proliferation of Mammalian Cardiomyocytes
Zhang, Y., Li, T., Lee, S.-T., Wawrowsky, K., Cheng, K., Galang, G., Malliaras, K. G., Abraham, M. R., Wang, C., & Marbán, E. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012559 · Cited by 200 · see citing works
Marqués‐Torrejón, M. Á., Porlan, E., Banito, A., Gómez-Ibarlucea, E., Lopez-Contreras, A. J., Fernández-Capetillo, Ó., Vidal, A., Gil, J., Torres, J., & Fariñas, I. (2012) · Cell stem cell · doi:10.1016/j.stem.2012.12.001 · Cited by 199 · see citing works
Liver Cancer Initiation Requires p53 Inhibition by CD44-Enhanced Growth Factor Signaling
Dhar, D., Antonucci, L., Nakagawa, H., Kim, J. Y., Glitzner, E., Caruso, S., Shalapour, S., Yang, L., Valasek, M. A., Lee, S., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.05.003 · Cited by 199 · see citing works
Targeting FAK in human cancer: from finding to first clinical trials
Golubovskaya, V. (2014) · Frontiers in bioscience · doi:10.2741/4236 · Cited by 197 · see citing works
Ji, J., Ng, S. H. S., Sharma, V., Neculai, D., Hussein, S. M. I., Sam, M., Trinh, Q. M., Church, G. M., McPherson, J. D., Nagy, A., et al. (2011) · Stem Cells · doi:10.1002/stem.1011 · Cited by 191 · see citing works
Reprogramming to pluripotency: stepwise resetting of the epigenetic landscape
Papp, B., & Plath, K. (2011) · Cell Research · doi:10.1038/cr.2011.28 · Cited by 188 · see citing works
Cai, J.-L., Li, W., Su, H.-X., Qin, D.-J., Yang, J.-Y., Zhu, F., Xu, J.-Y., He, W., Guo, X., Labuda, K., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.086389 · Cited by 184 · see citing works
Soufi, A., & Dalton, S. (2016) · Development · doi:10.1242/dev.142075 · Cited by 183 · see citing works
Mallanna, S. K., & Rizzino, A. (2010) · Developmental Biology · doi:10.1016/j.ydbio.2010.05.014 · Cited by 180 · see citing works
- Authors
- Hong, H., Takahashi, K., Ichisaka, T., Aoi, T., Kanagawa, O., Nakagawa, M., Okita, K., & Yamanaka, S.
- Affiliations
- Kyoto University (JP)
- RIKEN (JP)
- Gladstone Institutes (US)
- Corresponding author
- Yamanaka, Shinya
- Venue
- Nature
- Published
- 2009-08
- Volume
- 460
- Issue
- 7259
- Pages
- 1132-1135
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2917235
- OpenAlex
- W2081620485
- Cited by
- 1,301
- References
- 23
- Citations by year
- 2026: 13 · 2025: 16 · 2024: 25 · 2023: 29 · 2022: 44 · 2021: 51 · 2020: 41 · 2019: 56 · 2018: 63 · 2017: 59 · 2016: 78 · 2015: 88 · 2014: 116 · 2013: 117 · 2012: 168
- FWCI
- 67.71
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (U01HL100406)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- induced pluripotent stem cells, p53, p21, p53/p21 pathway, reprogramming efficiency, mouse embryonic fibroblasts, T cells, plasmid transfection, p53 target genes, tumorigenicity, Oct4, SOX2, KLF4, c-Myc
- MeSH terms
- Kruppel-Like Factor 4, Adult, Animals, Cell Differentiation, Embryo, Mammalian, Female, Fibroblasts, Humans, Male, Plasmids, T-Lymphocytes, Transfection, Tumor Suppressor Protein p53, Genes, myc, Oligonucleotide Array Sequence Analysis, Gene Silencing, Gene Expression Profiling, Pluripotent Stem Cells, Cyclin-Dependent Kinase Inhibitor p21, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
