Linking the p53 tumour suppressor pathway to somatic cell reprogramming
Open accessAbstract
Reprogramming somatic cells to induced pluripotent stem (iPS) cells has been accomplished by expressing pluripotency factors and oncogenes, but the low frequency and tendency to induce malignant transformation compromise the clinical utility of this powerful approach. We address both issues by investigating the mechanisms limiting reprogramming efficiency in somatic cells. Here we show that reprogramming factors can activate the p53 (also known as Trp53 in mice, TP53 in humans) pathway. Reducing signalling to p53 by expressing a mutated version of one of its negative regulators, by deleting or knocking down p53 or its target gene, p21 (also known as Cdkn1a), or by antagonizing reprogramming-induced apoptosis in mouse fibroblasts increases reprogramming efficiency. Notably, decreasing p53 protein levels enabled fibroblasts to give rise to iPS cells capable of generating germline-transmitting chimaeric mice using only Oct4 (also known as Pou5f1) and Sox2. Furthermore, silencing of p53 significantly increased the reprogramming efficiency of human somatic cells. These results provide insights into reprogramming mechanisms and suggest new routes to more efficient reprogramming while minimizing the use of oncogenes.
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Reducing p53 with shRNA makes cell reprogramming more efficient.
“Knocking down p53 by shRNA increased the efficiency of cell reprogramming.”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [79]
Activation of p53 helps explain why induced pluripotent stem cells are produced only rarely during reprogramming.
“Recently we, and others, showed that p53 activation contributed to the low frequency of generating induced pluripotent stem cells (iPS) during cell reprogramming [79,80].”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [79]
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Takahashi, K., & Yamanaka, S. (2006) · Cell · doi:10.1016/j.cell.2006.07.024 · Cited by 26,673 · see citing works
Induction 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
Induced 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
In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2
Vassilev, L. T., Vu, B. T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C., et al. (2004) · Science · doi:10.1126/science.1092472 · Cited by 4,661 · 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
Tumor suppressor p53 is a direct transcriptional activator of the human bax gene
Toshiyuki, M., & Reed, J. C. (1995) · Cell · doi:10.1016/0092-8674(95)90412-3 · Cited by 4,063 · see citing works
Reprogramming 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
Generation of Human Induced Pluripotent Stem Cells by Direct Delivery of Reprogramming Proteins
Kim, D., Kim, C.-H., Moon, J.-I., Chung, Y.-G., Chang, M.-Y., Han, B.-S., Ko, S., Yang, E., Cha, K. Y., Lanza, R., et al. (2009) · Cell stem cell · doi:10.1016/j.stem.2009.05.005 · Cited by 1,814 · see citing works
Zhang, Y., Xiong, Y., & Yarbrough, W. G. (1998) · Cell · doi:10.1016/s0092-8674(00)81401-4 · Cited by 1,626 · see citing works
A novel form of Epstein-Barr virus latency in normal B cells in vivo
Miyashita, E. M., Yang, B., Lam, K. M. C., Crawford, D., & Thorley‐Lawson, D. A. (1995) · Cell · doi:10.1016/0092-8674(95)90513-8 · Cited by 1,591 · see citing works
Pomerantz, J., Schreiber-Agus, N., Liégeois, N. J., Silverman, A., Alland, L., Chin, L., Potes, J., Chen, K., Orlow, I., Lee, H.-W., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81400-2 · Cited by 1,521 · see citing works
Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes
Aasen, T., Raya, A., Barrero, M. J., Garreta, E., Consiglio, A., Gonzalez, F., Vassena, R., Bilić, J., Pekarik, V., Tiscornia, G., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt.1503 · Cited by 1,423 · see citing works
Self-citationInduction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2
Huangfu, D., Osafune, K., Maehr, R., Guo, W., Eijkelenboom, A., Chen, S., Muhlestein, W. E., & Melton, D. A. (2008) · Nature Biotechnology · doi:10.1038/nbt.1502 · Cited by 1,342 · see citing works
A Chemical Inhibitor of p53 That Protects Mice from the Side Effects of Cancer Therapy
Komarov, P. G., Komarova, E. A., Kondratov, R. V., Christov-Tselkov, K., Coon, J. S., Chernov, M. V., & Gudkov, A. V. (1999) · Science · doi:10.1126/science.285.5434.1733 · Cited by 1,270 · see citing works
Development of a self-inactivating lentivirus vector
Miyoshi, H., Blömer, U., Takahashi, M., Gage, F. H., & Verma, I. M. (1998) · Journal of Virology · doi:10.1128/jvi.72.10.8150-8157.1998 · Cited by 1,196 · see citing works
Induction of pluripotent stem cells from fibroblast cultures
Takahashi, K., Okita, K., Nakagawa, M., & Yamanaka, S. (2007) · Nature Protocols · doi:10.1038/nprot.2007.418 · Cited by 1,080 · see citing works
Generation 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
Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2
Kamijo, T., Weber, J. D., Zambetti, G., Zindy, F., Roussel, M. F., & Sherr, C. J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.14.8292 · Cited by 899 · see citing works
Shi, Y., Desponts, C., Tae, J., Hahm, H. S., Schöler, H. R., & Ding, S. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.10.004 · Cited by 898 · see citing works
p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression
Lin, T., Chao, C., Saito, S., Mazur, S. J., Murphy, M. E., Appella, E., & Xu, Y. (2004) · Nature Cell Biology · doi:10.1038/ncb1211 · Cited by 859 · see citing works
Generation of Pluripotent Stem Cells from Neonatal Mouse Testis
Kanatsu-Shinohara, M., Inoue, K., Lee, J., Yoshimoto, M., Ogonuki, N., Miki, H., Baba, S., Kato, T., Kazuki, Y., Toyokuni, S., et al. (2004) · Cell · doi:10.1016/j.cell.2004.11.011 · Cited by 814 · see citing works
A core Klf circuitry regulates self-renewal of embryonic stem cells
Jiang, J., Chan, Y.-S., Loh, Y., Cai, J., Tong, G., Lim, C.-A., Robson, P., Zhong, S., & Ng, H. (2008) · Nature Cell Biology · doi:10.1038/ncb1698 · Cited by 746 · see citing works
Retrovirus-mediated gene transfer and expression cloning: powerful tools in functional genomics
Kitamura, T., Koshino, Y., Shibata, F., Oki, T., Nakajima, H., Nosaka, T., & Kumagai, H. (2003) · Experimental Hematology · doi:10.1016/j.exphem.2003.07.005 · Cited by 738 · see citing works
Wiznerowicz, M., & Trono, D. (2003) · Journal of Virology · doi:10.1128/jvi.77.16.8957-8951.2003 · Cited by 703 · see citing works
Retrovirus-mediated gene transfer and expression cloning: powerful tools in functional genomics
Kitamura, T., KOSHINO, Y., Shibata, F., et al. (2003) · Experimental Hematology · doi:10.1016/s0301-472x(03)00260-1 · Cited by 642 · see citing works
c-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
Rowland, B. D., Bernards, R., & Peeper, D. S. (2005) · Nature Cell Biology · doi:10.1038/ncb1314 · Cited by 583 · see citing works
Two 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
Tailoring to RB: tumour suppressor status and therapeutic response
Knudsen, E. S., & Knudsen, K. E. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2401 · Cited by 345 · see citing works
Shaulian, E., Zauberman, A., Ginsberg, D., & Oren, M. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.12.5581 · Cited by 341 · see citing works
Gonzãlez, F., Monasterio, M. B., Tiscornia, G., Pulido, N. M., Vassena, R., Batlle-Morera, L., Rodriguez-Piza, I., & Belmonte, J. C. (2009) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0901471106 · Cited by 324 · see citing works
Self-citationGeneration of Induced Pluripotent Stem Cells in the Absence of Drug Selection
Blelloch, R. H., Venere, M., Yen, J. S., & Ramalho‐Santos, M. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.08.008 · Cited by 278 · see citing works
Blelloch, R. H., Wang, Z., Meissner, A., Pollard, S. M., Smith, A. G., & Jaenisch, R. (2006) · Stem Cells · doi:10.1634/stemcells.2006-0050 · Cited by 277 · see citing works
From Bench to Bedside A Novel Technique of Acquiring OCT Images
Prati, F., Cera, M., Ramazzotti, V., Imola, F., Giudice, R., Giudice, M., Propris, S. D., & Albertucci, M. (2008) · Circulation Journal · doi:10.1253/circj.72.839 · Cited by 253 · see citing works
Marine, J.-C. W., Dyer, M. A., & Jochemsen, A. G. (2007) · Journal of Cell Science · doi:10.1242/jcs.03362 · Cited by 228 · see citing works
Foster, K. W., Ren, S., Louro, I. D., Lobo-Ruppert, S. M., McKie-Bell, P., Grizzle, W. E., Hayes, M., Broker, T. R., Chow, L. T., & Ruppert, J. M. (1999) · PubMed · Cited by 187 · see citing works
Guanine nucleotide biosynthesis is regulated by the cellular p53 concentration.
Sherley, J. L. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)54302-7 · Cited by 95 · see citing works
Wang, Y. V., Leblanc, M., Wade, M., Jochemsen, A. G., & Wahl, G. M. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.05.008 · Cited by 79 · see citing works
Self-citationMolecular cloning, sequencing, chromosomal localization and expression of mouse p21 (Waf1).
Huppi, K. E., Siwarski, D. F., Dosik, J. K., Michieli, P., Chedid, M., Reed, S. I., Mock, B. A., Givol, D., & Mushinski, J. F. (1994) · PubMed · Cited by 78 · see citing works
Antagonism of Myc functions by Arf
Cleveland, J. L., & Sherr, C. J. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.09.020 · Cited by 40 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Warren, L., Manos, P. D., Ahfeldt, T., Loh, Y.-H., Li, H., Lau, F., Ebina, W., Mandal, P. K., Smith, Z. D., Meissner, A., et al. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.08.012 · Cited by 2,662 · see citing works
The 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
Mutant p53 in Cancer: New Functions and Therapeutic Opportunities
Muller, P. A. J., & Vousden, K. H. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.01.021 · Cited by 1,545 · 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
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
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
Self-citationOncogenic 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
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
Soufi, A., Donahue, G., & Zaret, K. (2012) · Cell · doi:10.1016/j.cell.2012.09.045 · Cited by 888 · 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
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
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
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
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
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
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
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
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
Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state
Lapasset, L., Milhavet, O., Prieur, A., Besnard, E., Babled, A., Aït-Hamou, N., Leschik, J., Pellestor, F., Ramirez, J.-M., De Vos, J., et al. (2011) · Genes & Development · doi:10.1101/gad.173922.111 · Cited by 570 · see citing works
Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome
Liu, G.-H., Barkho, B. Z., Ruiz, S., Diep, D., Qu, J., Yang, S.-L., Panopoulos, A. D., Suzuki, K., Kurian, L., Walsh, C., et al. (2011) · Nature · doi:10.1038/nature09879 · Cited by 575 · see citing works
Self-citationSox2 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
Methionine Metabolism Regulates Maintenance and Differentiation of Human Pluripotent Stem Cells
Shiraki, N., Shiraki, Y., Tsuyama, T., Obata, F., Miura, M., Nagae, G., Aburatani, H., Kume, K., Endo, F., & Kume, S. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.03.017 · Cited by 514 · see citing works
Oncogenes and Tumor Suppressor GenesPreprint
Lee, E. Y., & Muller, W. J. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a003236 · Cited by 515 · 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
Self-citationDimitrova, N., Zamudio, J. R., Jong, R. M., Soukup, D., Resnick, R., Sarma, K., Ward, A. J., Raj, A., Lee, J. T., Sharp, P. A., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.04.025 · Cited by 445 · see citing works
Cellular plasticity and the neuroendocrine phenotype in prostate cancer
Davies, A. H., Beltran, H., & Zoubeidi, A. (2018) · Nature Reviews Urology · doi:10.1038/nrurol.2018.22 · Cited by 431 · see citing works
The p53 orchestra: Mdm2 and Mdmx set the tone
Wade, M., Wang, Y. V., & Wahl, G. M. (2010) · Trends in Cell Biology · doi:10.1016/j.tcb.2010.01.009 · Cited by 450 · see citing works
Self-citationExamination 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
The 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
Systemic 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
Zou, M., Toivanen, R., Mitrofanova, A., Floc’h, N., Hayati, S., Sun, Y., Magnen, C. L., Chester, D., Mostaghel, E. A., Califano, A., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-1174 · Cited by 380 · see citing works
miR-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
Tsai, C., Chen, Y.-J., Yew, T., Chen, L., Wang, J., Chiu, C., & Hung, S. (2010) · Blood · doi:10.1182/blood-2010-05-287508 · Cited by 376 · see citing works
Genetic and Epigenetic Variations in iPSCs: Potential Causes and Implications for Application
Liang, G., & Zhang, Y. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.07.001 · Cited by 368 · see citing works
Induced Pluripotent Stem Cells and Their Use in Human Models of Disease and Development
Karagiannis, P., Takahashi, K., Saito, M. K., Yoshida, Y., Okita, K., Watanabe, A., Inoue, H., Yamashita, J. K., Todani, M., Nakagawa, M., et al. (2018) · Physiological Reviews · doi:10.1152/physrev.00039.2017 · Cited by 367 · see citing works
Identification and Successful Negotiation of a Metabolic Checkpoint in Direct Neuronal Reprogramming
Gascón, S., Murenu, E., Masserdotti, G., Ortega, F., Russo, G. L., Petřík, D., Deshpande, A., Heinrich, C., Karow, M., Robertson, S. P., et al. (2015) · Cell stem cell · doi:10.1016/j.stem.2015.12.003 · Cited by 354 · see citing works
The circular RNA circBIRC6 participates in the molecular circuitry controlling human pluripotency
Yu, C.-Y., Li, T.-C., Wu, Y.-Y., Yeh, C.-H., Chiang, W., Chuang, C.-Y., & Kuo, H.-C. (2017) · Nature Communications · doi:10.1038/s41467-017-01216-w · Cited by 336 · see citing works
An Animal Model of MYC-Driven Medulloblastoma
Pei, Y., Moore, C. E., Wang, J., Tewari, A. K., Eroshkin, A. M., Cho, Y., Witt, H., Korshunov, A., Read, T., Sun, J., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2011.12.021 · Cited by 316 · 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
Self-citationWakao, S., Kitada, M., Kuroda, Y., Shigemoto, T., Matsuse, D., Akashi, H., Tanimura, Y., Tsuchiyama, K., Kikuchi, T., Goda, M., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1100816108 · Cited by 315 · see citing works
Acquired cancer stem cell phenotypes through Oct4-mediated dedifferentiation
Kumar, S. M., Liu, S.-J., Lu, H., Zhang, H., Zhang, P. J. L., Gimotty, P., Guerra, M., Guo, W., & Xu, X.-W. (2012) · Oncogene · doi:10.1038/onc.2011.656 · Cited by 330 · 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
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
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
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
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
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
Riggi, N., Suvà, M.-L., Vito, C. D., Provero, P., Stehle, J., Baumer, K., Cironi, L., Janiszewska, M., Petricevic, T., Suvà, D., et al. (2010) · Genes & Development · doi:10.1101/gad.1899710 · Cited by 279 · 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
Li, M., He, Y., Dubois, W., Wu, X., Shi, J., & Huang, J. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.01.020 · Cited by 264 · 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
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
Prigione, A., Rohwer, N., Hoffmann, S., Mlody, B., Drews, K., Bukowiecki, R., Blümlein, K., Wanker, E. E., Ralser, M., Cramer, T., et al. (2013) · Stem Cells · doi:10.1002/stem.1552 · Cited by 252 · see citing works
Direct lineage conversions: unnatural but useful?
Vierbuchen, T., & Wernig, M. (2011) · Nature Biotechnology · doi:10.1038/nbt.1946 · Cited by 259 · 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
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
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
Basal Cell Carcinomas Arise from Hair Follicle Stem Cells in Ptch1+/− Mice
Wang, G., Wang, J., Mancianti, M., & Epstein, E. H. (2011) · Cancer Cell · doi:10.1016/j.ccr.2010.11.007 · Cited by 225 · 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
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
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
The Use of Induced Pluripotent Stem Cells in Drug Development
Inoue, H., & Yamanaka, S. (2011) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2011.38 · Cited by 222 · see citing works
Cellular Differences in Protein Synthesis Regulate Tissue Homeostasis
Buszczak, M., Signer, R. A. J., & Morrison, S. J. (2014) · Cell · doi:10.1016/j.cell.2014.09.016 · Cited by 215 · 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
Hedgehog 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
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
Omole, A. E., & Fakoya, A. O. J. (2018) · PeerJ · doi:10.7717/peerj.4370 · Cited by 207 · 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
Swarbrick, A., Woods, S. L., Shaw, A., Balakrishnan, A., Phua, Y. W., Nguyen, A., Chanthery, Y. H., Lim, L., Ashton, L. J., Judson, R. L., et al. (2010) · Nature Medicine · doi:10.1038/nm.2227 · 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
Soufi, A., & Dalton, S. (2016) · Development · doi:10.1242/dev.142075 · Cited by 183 · 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
Targeting Programmed Cell Death Using Small‐Molecule Compounds to Improve Potential Cancer Therapy
Ke, B., Tian, M., Li, J., Liu, B., & He, G. (2016) · Medicinal Research Reviews · doi:10.1002/med.21398 · Cited by 188 · see citing works
Mosteiro, L., Pantoja, C., de Martino, A., & Serrano, M. (2018) · Aging Cell · doi:10.1111/acel.12711 · Cited by 182 · 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
Zunder, E. R., Lujan, E., Goltsev, Y., Wernig, M., & Nolan, G. P. (2015) · Cell stem cell · doi:10.1016/j.stem.2015.01.015 · Cited by 177 · see citing works
Molecular classification of prostate cancer using curated expression signatures
Markert, E. K., Mizuno, H., Vázquez, A., & Levine, A. J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1117029108 · Cited by 179 · 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
Induced Neuronal Cells: How to Make and Define a Neuron
Yang, N., Ng, Y. H., Pang, Z. P., Südhof, T. C., & Wernig, M. (2011) · Cell stem cell · doi:10.1016/j.stem.2011.11.015 · Cited by 180 · see citing works
Human and mouse adipose-derived cells support feeder-independent induction of pluripotent stem cells
Sugii, S., Kida, Y. S., Kawamura, T., Suzuki, J., Vassena, R., Yin, Y.-Q., Lutz, M. K., Berggren, W. T., Belmonte, J. C. I., & Evans, R. M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910172106 · Cited by 179 · see citing works
Self-citationCharacterization of pluripotent stem cells
Martí, M., Mulero, L., Pardo, C., Morera, C., Carrió, M., Laricchia‐Robbio, L., Esteban, C. R., & Belmonte, J. C. I. (2013) · Nature Protocols · doi:10.1038/nprot.2012.154 · Cited by 178 · see citing works
Self-citationStem cell therapy for type 1 diabetes mellitus
Aguayo-Mazzucato, C., & Bonner-Weir, S. (2010) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2009.274 · Cited by 184 · see citing works
Direct Neuronal Reprogramming: Achievements, Hurdles, and New Roads to Success
Gascón, S., Masserdotti, G., Russo, G. L., & Götz, M. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.06.011 · Cited by 177 · see citing works
Present and future challenges of induced pluripotent stem cells
Ohnuki, M., & Takahashi, K. (2015) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2014.0367 · Cited by 177 · see citing works
Aging and reprogramming: a two-way street
Mahmoudi, S., & Brunet, A. (2012) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2012.10.004 · Cited by 171 · see citing works
DNA Damage Responses in Human Induced Pluripotent Stem Cells and Embryonic Stem Cells
Momčilović, O., Knobloch, L., Fornsaglio, J. L., Varum, S., Easley, C. A., & Schatten, G. P. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013410 · Cited by 174 · see citing works
iPS cells: A source of cardiac regeneration
Yoshida, Y., & Yamanaka, S. (2010) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2010.10.026 · Cited by 173 · see citing works
Yoshida, Y., & Yamanaka, S. (2010) · Circulation · doi:10.1161/circulationaha.109.881433 · Cited by 171 · see citing works
PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype
Duan, S., Yuan, G., Liu, X., Ren, R., Li, J., Zhang, W., Wu, J., Xu, X., Fu, L., Li, Y., et al. (2015) · Nature Communications · doi:10.1038/ncomms10068 · Cited by 169 · see citing works
Self-citationGingival Fibroblasts as a Promising Source of Induced Pluripotent Stem Cells
Egusa, H., Okita, K., Kayashima, H., Yu, G., Fukuyasu, S., Saeki, M., Matsumoto, T., Yamanaka, S., & Yatani, H. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012743 · Cited by 166 · see citing works
p53 loss promotes acute myeloid leukemia by enabling aberrant self-renewalPreprint
Zhao, Z., Zuber, J. A., Díaz-Flores, E., Lintault, L., Kogan, S. C., Shannon, K., & Lowe, S. W. (2010) · Genes & Development · doi:10.1101/gad.1940710 · Cited by 167 · see citing works
- Authors
- Kawamura, T., Suzuki, J., Wang, Y. V., Menendez, S., Morera, L. B., Raya, A., Wahl, G. M., & Belmonte, J. C. I.
- Affiliations
- Salk Institute for Biological Studies (US)
- Corresponding author
- Wahl, Geoffrey M.
- Belmonte, Juan Carlos Izpisúa
- Venue
- Nature
- Published
- 2009-08
- Volume
- 460
- Issue
- 7259
- Pages
- 1140-1144
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2735889
- OpenAlex
- W2070672434
- Cited by
- 1,115
- References
- 40
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 30 · 2023: 34 · 2022: 31 · 2021: 36 · 2020: 29 · 2019: 41 · 2018: 55 · 2017: 60 · 2016: 65 · 2015: 77 · 2014: 96 · 2013: 111 · 2012: 136
- FWCI
- 57.10
- 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)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R33HL088293)
- National Cancer Institute (R01CA100845, R01CA061449)
- 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
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- p53, somatic cell reprogramming, induced pluripotent stem cells, Oct4, SOX2, p21, Nutlin-3, reprogramming efficiency, malignant transformation, fibroblasts, oncogenes, apoptosis
- MeSH terms
- Animals, Cells, Cultured, Embryo, Mammalian, Female, Fibroblasts, Humans, Male, Mice, Inbred C57BL, Down-Regulation, Keratinocytes, Tumor Suppressor Protein p53, Pluripotent Stem Cells, Cyclin-Dependent Kinase Inhibitor p21, Mice, Cellular Reprogramming
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