Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations
Open accessAbstract
Human pluripotent stem cells (hPS cells) can self-renew indefinitely, making them an attractive source for regenerative therapies. This expansion potential has been linked with the acquisition of large copy number variants that provide mutated cells with a growth advantage in culture. The nature, extent and functional effects of other acquired genome sequence mutations in cultured hPS cells are not known. Here we sequence the protein-coding genes (exomes) of 140 independent human embryonic stem cell (hES cell) lines, including 26 lines prepared for potential clinical use. We then apply computational strategies for identifying mutations present in a subset of cells in each hES cell line. Although such mosaic mutations were generally rare, we identified five unrelated hES cell lines that carried six mutations in the TP53 gene that encodes the tumour suppressor P53. The TP53 mutations we observed are dominant negative and are the mutations most commonly seen in human cancers. We found that the TP53 mutant allelic fraction increased with passage number under standard culture conditions, suggesting that the P53 mutations confer selective advantage. We then mined published RNA sequencing data from 117 hPS cell lines, and observed another nine TP53 mutations, all resulting in coding changes in the DNA-binding domain of P53. In three lines, the allelic fraction exceeded 50%, suggesting additional selective advantage resulting from the loss of heterozygosity at the TP53 locus. As the acquisition and expansion of cancer-associated mutations in hPS cells may go unnoticed during most applications, we suggest that careful genetic characterization of hPS cells and their differentiated derivatives be carried out before clinical use.
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Six specific variants in TP53 have been identified in several hPSC lines.
“and six specific variants in TP53 have been identified in several hPSC lines.165”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [165]
For pluripotent stem cells (ESCs or iPSCs), there appears to be a selection advantage for mutations of some oncogenes, in particular TP53 and BCOR, which can become fixed in culture.
“For pluripotent stem cells—embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs)—there appears to be a selection advantage for mutations of some oncogenes, in particular for TP53 and BCOR, which can become fixed in culture74,75.”
From How to design preclinical studies in nanomedicine and cell therapy to maximize the prospects of clinical translation (2018) · cites this paper as [74]
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Robinson, J. T., Thorvaldsdóttir, H., Winckler, W., Guttman, M., Lander, E. S., Getz, G., & Mesirov, J. P. (2011) · Nature Biotechnology · doi:10.1038/nbt.1754 · Cited by 15,390 · see citing works
Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., & Salzberg, S. L. (2013) · Genome Biology · doi:10.1186/gb-2013-14-4-r36 · Cited by 12,668 · see citing works
A framework for variation discovery and genotyping using next-generation DNA sequencing data
DePristo, M. A., Banks, E., Poplin, R. E., Garimella, K. V., Maguire, J., Hartl, C., Philippakis, A., del Angel, G., Rivas, M. A., Hanna, M., et al. (2011) · Nature Genetics · doi:10.1038/ng.806 · Cited by 11,216 · see citing works
Analysis of protein-coding genetic variation in 60,706 humans
Exome Aggregation Consortium, Lek, M., Karczewski, K. J., Minikel, E. V., Samocha, K. E., Banks, E., Fennell, T., O’Donnell-Luria, A. H., Ware, J. S., Hill, A. J., et al. (2016) · Nature · doi:10.1038/nature19057 · Cited by 9,587 · see citing works
Self-citationdbSNP: the NCBI database of genetic variation
Sherry, S. T. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.1.308 · Cited by 7,502 · see citing works
Vogelstein, B., Lane, D., & Levine, A. J. (2000) · Nature · doi:10.1038/35042675 · Cited by 6,607 · see citing works
Age-related clonal hematopoiesis associated with adverse outcomes
Jaiswal, S., Fontanillas, P., Flannick, J., Manning, A., Grauman, P. V., Mar, B. G., Lindsley, R. C., Mermel, C. H., Burtt, N., Chavez, A., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1408617 · Cited by 4,841 · see citing works
Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence
Genovese, G., Kähler, A. K., Handsaker, R. E., Lindberg, J., Rose, S. A., Bakhoum, S. F., Chambert, K., Mick, E., Neale, B. M., Fromer, M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1409405 · Cited by 3,531 · see citing works
Self-citationHigh-throughput droplet digital PCR system for absolute quantitation of DNA copy number
Hindson, B. J., Ness, K. D., Masquelier, D. A., Belgrader, P., Heredia, N. J., Makarewicz, A. J., Bright, I. J., Lucero, M. Y., Hiddessen, A. L., Legler, T. C., et al. (2011) · Analytical Chemistry · doi:10.1021/ac202028g · Cited by 2,792 · see citing works
Crystal Structure of a p53 Tumor Suppressor-DNA Complex: Understanding Tumorigenic Mutations
Cho, Y., Gorina, S., Jeffrey, P. D., & Pavletich, N. P. (1994) · Science · doi:10.1126/science.8023157 · Cited by 2,559 · see citing works
COSMIC: exploring the world's knowledge of somatic mutations in human cancer
Forbes, S. A., Beare, D. M., Gunasekaran, P., Leung, K., Bindal, N., Boutselakis, H., Ding, M., Bamford, S., Cole, C. G., Ward, S. A., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku1075 · Cited by 2,261 · see citing works
A unique chromatin signature uncovers early developmental enhancers in humans
Rada-Iglesias, A., Bajpai, R., Swigut, T., Brugmann, S. A., Flynn, R. A., & Wysocka, J. (2011) · Nature · doi:10.1038/nature09692 · Cited by 2,233 · see citing works
Prescribing Personalized Nutrition for Cardiovascular Health: Are We Ready?
Juma, S., Imrhan, V., Vijayagopal, P., & Prasad, C. (2014) · Lifestyle Genomics · doi:10.1159/000370213 · Cited by 1,905 · see citing works
The complete genome of an individual by massively parallel DNA sequencing
Wheeler, D. A., Srinivasan, M., Egholm, M., Shen, Y., Chen, L., McGuire, A., He, W., Chen, Y.-J., Makhijani, V., Roth, G. T., et al. (2008) · Nature · doi:10.1038/nature06884 · Cited by 1,838 · see citing works
Wang, K., Li, M., Hadley, D., Liu, R., Glessner, J., Grant, S. F. A., Hakonarson, H., & Bucan, M. (2007) · Genome Research · doi:10.1101/gr.6861907 · Cited by 1,792 · see citing works
Chemically defined conditions for human iPSC derivation and culture
Chen, G., Gulbranson, D. R., Hou, Z., Bolin, J. M., Ruotti, V., Probasco, M. D., Smuga-Otto, K., Howden, S. E., Diol, N. R., Propson, N. E., et al. (2011) · Nature Methods · doi:10.1038/nmeth.1593 · Cited by 1,447 · see citing works
Somatic mutation in cancer and normal cells
Martincorena, I., & Campbell, P. J. (2015) · Science · doi:10.1126/science.aab4082 · Cited by 1,396 · see citing works
Schwartz, S. D., Regillo, C. D., Lam, B. L., Eliott, D., Rosenfeld, P. J., Gregori, N. Z., Hubschman, J.-P., Davis, J. L., Heilwell, G., Spirn, M., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(14)61376-3 · Cited by 1,327 · see citing works
BigWig and BigBed: enabling browsing of large distributed datasets
Kent, W. J., Zweig, A. S., Barber, G. P., Hinrichs, A. S., & Karolchik, D. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq351 · Cited by 1,268 · see citing works
Derivation of human embryonic stem cells in defined conditions
Ludwig, T. E., Levenstein, M. E., Jones, J. M., Berggren, W. T., Mitchen, E. R., Frane, J. L., Crandall, L. J., Daigh, C. A., Conard, K. R., Piekarczyk, M. S., et al. (2006) · Nature Biotechnology · doi:10.1038/nbt1177 · Cited by 1,114 · see citing works
Characterization of human embryonic stem cell lines by the International Stem Cell Initiative
Initiative, T. I. S. C. (2007) · Nature Biotechnology · doi:10.1038/nbt1318 · Cited by 1,078 · see citing works
A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity
Marión, R. M., Strati, K., Li, H., Murga, M., Blanco, R., Ortega, S., Fernandez-Capetillo, O., Serrano, M., & Blasco, M. A. (2009) · Nature · doi:10.1038/nature08287 · Cited by 1,028 · see citing works
Laurent, L. C., Ulitsky, I., Slavin, I., Tran, H., Schork, A., Morey, R., Lynch, C., Harness, J. V., Lee, S., Barrero, M. J., et al. (2011) · Cell stem cell · doi:10.1016/j.stem.2010.12.003 · Cited by 890 · see citing works
Bouaoun, L., Sonkin, D., Ardin, M., Hollstein, M., Byrnes, G., Zavadil, J., & Olivier, M. (2016) · Human Mutation · doi:10.1002/humu.23035 · Cited by 730 · see citing works
5-Methylcytosine as an Endogenous Mutagen in the Human LDL Receptor and p53 Genes
Rideout, W. M., Coetzee, G. A., Olumi, A. F., & Jones, P. A. (1990) · Science · doi:10.1126/science.1697983 · Cited by 640 · see citing works
International Cancer Genome Consortium Data Portal--a one-stop shop for cancer genomics data
Zhang, J., Baran, J., Cros, A., Guberman, J. M., Haider, S. A., Hsu, J. C., Liang, Y., Rivkin, E., Wang, J., Whitty, B. R., et al. (2011) · Database · doi:10.1093/database/bar026 · Cited by 637 · see citing works
Initiative, T. I. S. C. (2011) · Nature Biotechnology · doi:10.1038/nbt.2051 · Cited by 570 · see citing works
Malkin, D. M. (2011) · Genes & Cancer · doi:10.1177/1947601911413466 · Cited by 507 · see citing works
Jun, G., Flickinger, M., Hetrick, K. N., Romm, J. M., Doheny, K. F., Abecasis, G. R., Boehnke, M., & Kang, H. M. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.09.004 · Cited by 484 · 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
Willis, A. C., Jung, E. J., Wakefield, T., & Chen, X. (2004) · Oncogene · doi:10.1038/sj.onc.1207396 · Cited by 334 · see citing works
Good manufacturing practice and clinical-grade human embryonic stem cell lines.
Unger, C., Skottman, H., Blomberg, P., Dilber, M. S., & Hovatta, O. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn079 · Cited by 269 · see citing works
Xie, R., Everett, L., Lim, H., Patel, N., Schug, J., Kroon, E. J., Kelly, O. G., Wang, A., D'Amour, K., Robins, A., et al. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2012.11.023 · Cited by 240 · see citing works
RIKEN suspends first clinical trial involving induced pluripotent stem cells
Garber, K. (2015) · Nature Biotechnology · doi:10.1038/nbt0915-890 · Cited by 215 · see citing works
Avery, S., Hirst, A. J., Baker, D., Lim, C. Y., Alagaratnam, S., Skotheim, R. I., Lothe, R. A., Pera, M. F., Colman, A., Robson, P., et al. (2013) · Stem Cell Reports · doi:10.1016/j.stemcr.2013.10.005 · Cited by 161 · see citing works
Merkle, F. T., Neuhausser, W. M., Santos, D., Valen, E., Gagnon, J. A., Maas, K., Sandoe, J., Schier, A. F., & Eggan, K. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.04.007 · Cited by 152 · see citing works
Self-citationDetecting Genetic Mosaicism in Cultures of Human Pluripotent Stem Cells
Baker, D., Hirst, A. J., Gokhale, P. J., Juárez, M. A., Williams, S., Wheeler, M., Bean, K., Allison, T. F., Moore, H. D. M., Andrews, P. W., et al. (2016) · Stem Cell Reports · doi:10.1016/j.stemcr.2016.10.003 · Cited by 149 · see citing works
Nguyen, H. T., Geens, M., Mertzanidou, A., Jacobs, K., Heirman, C., Breckpot, K., & Spits, C. (2013) · Molecular Human Reproduction · doi:10.1093/molehr/gat077 · Cited by 111 · see citing works
Ganna, A., Genovese, G., Howrigan, D. P., Byrnes, A., Kurki, M., Zekavat, S. M., Whelan, C. W., Kals, M., Nivard, M. G., Bloemendal, A., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4404 · Cited by 101 · see citing works
Self-citationHuman Intestinal Tissue with Adult Stem Cell Properties Derived from Pluripotent Stem Cells
Forster, R. E., Chiba, K., Schaeffer, L., Regalado, S. G., Lai, C. S., Gao, Q., Kiani, S., Farin, H. F., Clevers, H. C., Cost, G. J., et al. (2014) · Stem Cell Reports · doi:10.1016/j.stemcr.2014.05.001 · Cited by 88 · see citing works
Heterogeneity of Li-Fraumeni Syndrome links to unequal gain-of-function effects of p53 mutations
Xu, J., Qian, J., Hu, Y., Wang, J., Zhou, X., Chen, H., & Fang, J. (2014) · Scientific Reports · doi:10.1038/srep04223 · Cited by 76 · see citing works
Amir, H., Touboul, T., Sabatini, K., Chhabra, D., Garitaonandia, I., Loring, J. F., Morey, R. E., & Laurent, L. C. (2016) · Stem Cells · doi:10.1002/stem.2550 · Cited by 38 · see citing works
Amir, H., Sabatini, K., Chhabra, D., Morey, R. E., & Laurent, L. C. (2016) · Fertility and Sterility · doi:10.1016/j.fertnstert.2016.07.1033 · Cited by 6 · see citing works
Culturing human pluripotent stem cells from diverse culture histories
Carver, A., Merkle, F. T., & Eggan, K. C. (2017) · Protocol Exchange · doi:10.1038/protex.2017.087 · Cited by 1 · see citing works
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Flagged first, then by citations
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Sorted by citations
Kastenhuber, E. R., & Lowe, S. W. (2017) · Cell · doi:10.1016/j.cell.2017.08.028 · Cited by 1,906 · 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
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
Transcription factor-mediated differentiation of human iPSCs into neurons
Fernandopulle, M. S., Prestil, R., Grunseich, C., Wang, C., Gan, L., & Ward, M. E. (2018) · Current Protocols in Cell Biology · doi:10.1002/cpcb.51 · Cited by 461 · see citing works
Understanding the complexity of p53 in a new era of tumor suppression
Liu, Y., Su, Z., Tavana, O., & Gu, W. J. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.04.009 · Cited by 519 · see citing works
RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues
Yizhak, K., Aguet, F., Kim, J., Hess, J. M., Kübler, K., Grimsby, J., Frazer, R., Zhang, H., Haradhvala, N. J., Rosebrock, D., et al. (2019) · Science · doi:10.1126/science.aaw0726 · Cited by 500 · see citing works
Current Challenges of iPSC-Based Disease Modeling and Therapeutic Implications
Doss, M. X., & Sachinidis, A. (2019) · Cells · doi:10.3390/cells8050403 · Cited by 467 · see citing works
Volpato, V., & Webber, C. (2020) · Disease Models & Mechanisms · doi:10.1242/dmm.042317 · Cited by 379 · see citing works
Sharma, R., Khristov, V., Rising, A. C., Jha, B. S., Dejene, R., Hotaling, N. A., Li, Y., Stoddard, J., Stankewicz, C., Wan, Q., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aat5580 · Cited by 362 · see citing works
Gain-of-function mutant p53 in cancer progression and therapy
Zhang, C., Liu, J., Xu, D., Zhang, T., Hu, W., & Feng, Z. (2020) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjaa040 · Cited by 339 · see citing works
Metabolic signatures of cancer cells and stem cells
Intlekofer, A. M., & Finley, L. W. S. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0032-0 · Cited by 322 · see citing works
A reference human induced pluripotent stem cell line for large-scale collaborative studies
Pantazis, C. B., Yang, A., Lara, E., McDonough, J. A., Blauwendraat, C., Peng, L., Oguro, H., Kanaujiya, J., Zou, J., Sebesta, D., et al. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2022.11.004 · Cited by 310 · see citing works
Self-citationEpigenetic resetting of human pluripotency
Guo, G., von Meyenn, F., Rostovskaya, M., Clarke, J., Dietmann, S., Baker, D., Sahakyan, A., Myers, S., Bertone, P., Reik, W., et al. (2017) · Development · doi:10.1242/dev.146811 · Cited by 319 · see citing works
The future of stem cell therapies for Parkinson disease
Parmar, M., Grealish, S., & Henchcliffe, C. (2020) · Nature reviews. Neuroscience · doi:10.1038/s41583-019-0257-7 · Cited by 314 · see citing works
Somatic Cell Nuclear Transfer Reprogramming: Mechanisms and Applications
Matoba, S., & Zhang, Y. (2018) · Cell stem cell · doi:10.1016/j.stem.2018.06.018 · Cited by 306 · see citing works
Insights into the Secretome of Mesenchymal Stem Cells and Its Potential Applications
Eleuteri, S., & Fierabracci, A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20184597 · Cited by 302 · see citing works
Next-generation stem cells — ushering in a new era of cell-based therapies
Kimbrel, E. A., & Lanza, R. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0064-x · Cited by 280 · see citing works
Quality Control Guidelines for Clinical-Grade Human Induced Pluripotent Stem Cell Lines
Sullivan, S. K., Stacey, G. N., Akazawa, C., Aoyama, N., Baptista, R. P., Bedford, P., Griscelli, A. B., Chandra, A., Elwood, N. J., Girard, M., et al. (2018) · Regenerative Medicine · doi:10.2217/rme-2018-0095 · Cited by 265 · see citing works
Quantification of subclonal selection in cancer from bulk sequencing data
Williams, M. J., Werner, B., Heide, T., Curtis, C. N., Barnes, C. P., Sottoriva, A., & Graham, T. A. (2018) · Nature Genetics · doi:10.1038/s41588-018-0128-6 · Cited by 266 · see citing works
Stem Cells in the Treatment of Disease.
Blau, H., & Daley, G. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1716145 · Cited by 182 · see citing works
Neurogenesis in aging and age-related neurodegenerative diseases
Čulig, L., Chu, X., & Bohr, V. A. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101636 · Cited by 229 · see citing works
Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes
Hogrebe, N. J., Ishahak, M., & Millman, J. R. (2023) · Cell Stem Cell · doi:10.1016/j.stem.2023.04.002 · Cited by 210 · 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
Wang, B., Iriguchi, S., Waseda, M., Ueda, N., Ueda, T., Xu, H., Minagawa, A., Ishikawa, A., Yano, H., Ishi, T., et al. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00730-z · Cited by 189 · see citing works
Advances in regenerative therapy: A review of the literature and future directions
Ntege, E. H., Sunami, H., & Shimizu, Y. (2020) · Regenerative Therapy · doi:10.1016/j.reth.2020.01.004 · Cited by 197 · see citing works
Regenerating Eye Tissues to Preserve and Restore Vision
Stern, J. H., Tian, Y. I., Funderburgh, J. L., Pellegrini, G., Zhang, K., Goldberg, J. L., Ali, R. R., Young, M. J., Xie, Y., & Temple, S. (2018) · Cell stem cell · doi:10.1016/j.stem.2018.05.013 · Cited by 189 · see citing works
Song, B., Cha, Y., Ko, S., Jeon, J., Lee, N., Seo, H., Park, K., Lee, I., Lopes, C., Feitosa, M., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci130767 · Cited by 189 · see citing works
Gasparini, S. J., Llonch, S., Borsch, O., & Ader, M. (2018) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2018.11.001 · Cited by 185 · see citing works
Chen, Y., Tristan, C. A., Chen, L., Jovanovic, V. M., Malley, C. E., Chu, P., Ryu, S., Deng, T., Ormanoglu, P., Tao, D., et al. (2021) · Nature Methods · doi:10.1038/s41592-021-01126-2 · Cited by 173 · see citing works
Ioannidis, J. P. A., Kim, B. Y. S., & Trounson, A. (2018) · Nature Biomedical Engineering · doi:10.1038/s41551-018-0314-y · Cited by 175 · see citing works
Defining essential genes for human pluripotent stem cells by CRISPR–Cas9 screening in haploid cells
Yilmaz, A., Peretz, M., Aharony, A., Sagi, I., & Benvenisty, N. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0088-1 · Cited by 139 · see citing works
Self-citationHuman-specific genetics: new tools to explore the molecular and cellular basis of human evolution
Pollen, A. A., Kilik, U., Lowe, C. B., & Camp, J. G. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-022-00568-4 · Cited by 157 · see citing works
Pereira, J. D., DuBreuil, D. M., Devlin, A., Held, A., Sapir, Y., Berezovski, E., Hawrot, J., Dorfman, K., Chander, V., & Wainger, B. J. (2021) · Nature Communications · doi:10.1038/s41467-021-24776-4 · Cited by 155 · see citing works
Poetsch, M. S., Strano, A., & Guan, K. (2022) · Stem Cells · doi:10.1093/stmcls/sxac020 · Cited by 144 · see citing works
Pluripotent Stem Cell-based therapy for Parkinson’s disease: current status and future prospects
Sonntag, K. C., Song, B., Lee, N., Jung, J., Cha, Y.-G., Leblanc, P., Neff, C., Kong, S., Carter, B., Schweitzer, J. S., et al. (2018) · Progress in neurobiology · doi:10.1016/j.pneurobio.2018.04.005 · Cited by 127 · see citing works
Best Practices for Translational Disease Modeling Using Human iPSC-Derived Neurons
Engle, S. J., Blaha, L. C., & Kleiman, R. J. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.033 · Cited by 141 · see citing works
Stem Cells, Genome Editing, and the Path to Translational Medicine
Soldner, F., & Jaenisch, R. (2018) · Cell · doi:10.1016/j.cell.2018.09.010 · Cited by 139 · see citing works
Thompson, O., von Meyenn, F., Hewitt, Z., Alexander, J. J., Wood, A., Weightman, R., Gregory, S., Krueger, F., Andrews, S., Barbaric, I., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15271-3 · Cited by 140 · see citing works
Yoshida, S., Kato, T. M., Sato, Y., Umekage, M., Ichisaka, T., Tsukahara, M., Takasu, N., & Yamanaka, S. (2022) · i Medicina · doi:10.1016/j.medj.2022.10.003 · Cited by 118 · see citing works
Assessing the Safety of Human Pluripotent Stem Cells and Their Derivatives for Clinical Applications
Andrews, P. W., Ben‐David, U., Benvenisty, N., Coffey, P. J., Eggan, K. C., Knowles, B. B., Nagy, A., Pera, M. F., Reubinoff, B. E., Rugg‐Gunn, P. J., et al. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.05.029 · Cited by 132 · see citing works
Self-citationLong-term safety of human retinal progenitor cell transplantation in retinitis pigmentosa patients
Liu, Y., Chen, S. J., Li, S., Qu, L. H., Meng, X. H., Wang, Y. H., Xu, H., Liang, Z. Q., & Yin, Z. Q. (2017) · Stem Cell Research & Therapy · doi:10.1186/s13287-017-0661-8 · Cited by 129 · see citing works
Mair, B., Tomic, J., Masud, S. N., Tonge, P. J., Weiss, A., Ušaj, M., Tong, A. H. Y., Kwan, J. J., Brown, K. R., Titus, E., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.02.041 · Cited by 123 · see citing works
Assou, S., Girault, N., Plinet, M., Bouckenheimer, J., Sansac, C., Combe, M., Mianné, J., Bourguignon, C., Fieldès, M., Ahmed, E., et al. (2020) · Stem Cell Reports · doi:10.1016/j.stemcr.2019.12.004 · Cited by 130 · see citing works
Lung cancer stem cells—Origin, characteristics and therapy
Prabavathy, D., Swarnalatha, Y., & Ramadoss, N. (2018) · Stem Cell Investigation · doi:10.21037/sci.2018.02.01 · Cited by 125 · see citing works
Insights into pancreatic islet cell dysfunction from type 2 diabetes mellitus genetics
Krentz, N. A. J., & Gloyn, A. L. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0325-0 · Cited by 128 · see citing works
The mutational impact of culturing human pluripotent and adult stem cells
Kuijk, E., Jager, M., van der Roest, B., Locati, M. D., Van Hoeck, A., Korzelius, J., Janssen, R., Besselink, N., Boymans, S., van Boxtel, R., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16323-4 · Cited by 124 · see citing works
Genome-wide CRISPR screen for Zika virus resistance in human neural cells
Li, Y., Muffat, J., Omer, A., Keys, H. R., Lungjangwa, T., Bosch, I., Khan, M., Virgilio, M., Gehrke, L., Sabatini, D. M., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1900867116 · Cited by 124 · see citing works
A comprehensive resource for induced pluripotent stem cells from patients with primary tauopathies
Karch, C. M., Kao, A. W., Karydas, A., Onanuga, K., Martinez, R., Argouarch, A., Wang, C., Huang, C., Sohn, P. D., Bowles, K. R., et al. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2019.09.006 · Cited by 119 · see citing works
Variability of human pluripotent stem cell lines
Ortmann, D., & Vallier, L. (2017) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2017.07.004 · Cited by 117 · see citing works
Rouhani, F. J., Zou, X., Danecek, P., Badja, C., Amarante, T. D., Koh, G., Wu, Q., Memari, Y., Durbin, R., Martincorena, I., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01147-3 · Cited by 105 · see citing works
Cellular Pliancy and the Multistep Process of Tumorigenesis
Puisieux, A., Pommier, R. M., Morel, A., & Lavial, F. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.01.007 · Cited by 108 · see citing works
Martin, R. M., Fowler, J. L., Cromer, M., Lesch, B., Ponce, E., Uchida, N., Nishimura, T., Porteus, M. H., & Loh, K. (2020) · Nature Communications · doi:10.1038/s41467-020-16455-7 · Cited by 100 · see citing works
Clonal hematopoiesis, somatic mosaicism, and age-associated disease
Evans, M. A., & Walsh, K. (2022) · Physiological Reviews · doi:10.1152/physrev.00004.2022 · Cited by 105 · see citing works
Epigenetic aberrations in human pluripotent stem cells
Bar, S., & Benvenisty, N. (2019) · The EMBO Journal · doi:10.15252/embj.2018101033 · Cited by 105 · see citing works
Self-citationImproving homology-directed repair efficiency in human stem cells.
Skarnes, W., Pellegrino, E., & McDonough, J. (2019) · Methods · doi:10.1016/j.ymeth.2019.06.016 · Cited by 91 · see citing works
Acquired genetic changes in human pluripotent stem cells: origins and consequences
Halliwell, J. A., Barbaric, I., & Andrews, P. W. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00292-z · Cited by 101 · see citing works
Advances of Schwann cells in peripheral nerve regeneration: From mechanism to cell therapy
Wei, C., Guo, Y., Ci, Z., Li, M., Zhang, Y., & Zhou, Y. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116645 · Cited by 106 · see citing works
Vögtle, F. ‐., Brändl, B., Larson, A. A., Pendziwiat, M., Friederich, M. W., White, S. M., Basinger, A., Küçükköse, C., Muhle, H., Jähn, J. A., et al. (2018) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2018.02.014 · Cited by 100 · see citing works
Antiinflammatory activity of ANGPTL4 facilitates macrophage polarization to induce cardiac repair
Cho, D. I., Kang, H., Jeon, J. H., Eom, G. H., Cho, H. H., Kim, M. R., Cho, M., Jeong, H.-Y., Cho, H. C., Hong, M. H., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.125437 · Cited by 97 · see citing works
Aguado, J., Chaggar, H. K., Gómez‐Inclán, C., Shaker, M. R., Leeson, H. C., Mackay‐Sim, A., & Wolvetang, E. J. (2021) · Aging Cell · doi:10.1111/acel.13468 · Cited by 92 · see citing works
Engineered and banked iPSCs for advanced NK- and T-cell immunotherapies
Cichocki, F. M., van der Stegen, S. J. C., & Miller, J. S. (2022) · Blood · doi:10.1182/blood.2022016205 · Cited by 95 · see citing works
iPS-Cell Technology and the Problem of Genetic Instability—Can It Ever Be Safe for Clinical Use?
Attwood, S. W., & Edel, M. J. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8030288 · Cited by 97 · see citing works
Grattoni, A., Korbutt, G., Tomei, A. A., García, A. J., Pepper, A. R., Stabler, C., Brehm, M., Papas, K., Citro, A., Shirwan, H., et al. (2025) · Nature Reviews Endocrinology · doi:10.1038/s41574-024-01029-0 · Cited by 92 · see citing works
Sharma, R., Bose, D., Maminishkis, A., & Bharti, K. (2020) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010919-023245 · Cited by 91 · see citing works
D’Antonio, M., Benaglio, P., Jakubosky, D. A., Greenwald, W. W. Y., Matsui, H., Donovan, M. K. R., Li, H., Smith, E. N., D’Antonio‐Chronowska, A., & Frazer, K. A. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.06.091 · Cited by 87 · see citing works
Midbrain organoids with an SNCA gene triplication model key features of synucleinopathy
Mohamed, N., Sirois, J., Ramamurthy, J., Mathur, M., Lépine, P., Deneault, É., Maussion, G., Nicouleau, M., Chen, C. X. ‐., Abdian, N., et al. (2021) · Brain Communications · doi:10.1093/braincomms/fcab223 · Cited by 89 · see citing works
Cederquist, G., Tchieu, J. H., Callahan, S. J., Ramnarine, K., Ryan, S. D., Zhang, C., Rittenhouse, C. A., Zeltner, N., Chung, S. Y., Zhou, T., et al. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.06.004 · Cited by 85 · see citing works
Wang, B., Wang, H., Zhang, M., Ji, R., Wei, J., Xin, Y., & Jiang, X. M. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15479 · Cited by 86 · see citing works
Need for high-resolution Genetic Analysis in iPSC: Results and Lessons from the ForIPS Consortium
Popp, B., Krumbiegel, M., Grosch, J., Sommer, A., Uebe, S., Kohl, Z., Plötz, S., Farrell, M., Trautmann, U., Kraus, C. S., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-35506-0 · Cited by 85 · see citing works
The consequences of recurrent genetic and epigenetic variants in human pluripotent stem cells
Andrews, P. W., Barbaric, I., Benvenisty, N., Draper, J. S., Ludwig, T. E., Merkle, F. T., Sato, Y., Spits, C., Stacey, G. N., Wang, H., et al. (2022) · Cell stem cell · doi:10.1016/j.stem.2022.11.006 · Cited by 86 · see citing works
Self-citationZhang, H., Xu, J., Long, Y., Maimaitijiang, A., Su, Z., Li, W., & Li, J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252312928 · Cited by 92 · see citing works
Modeling cell-autonomous motor neuron phenotypes in ALS using iPSCs
Hawrot, J., Imhof, S., & Wainger, B. J. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104680 · Cited by 74 · see citing works
DNA damage contributes to neurotoxic inflammation in Aicardi-Goutières syndrome astrocytes
Giordano, A. M. S., Luciani, M., Gatto, F., Abou Alezz, M., Beghè, C., Della Volpe, L., Migliara, A., Valsoni, S., Genua, M., Dzieciatkowska, M., et al. (2022) · Journal of Experimental Medicine · doi:10.1084/jem.20211121 · Cited by 76 · see citing works
Zhang, C., Lee, H. J., Shrivastava, A., Wang, R., McQuiston, T. J., Challberg, S. S., Pollok, B. A., & Wang, T. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.09.072 · Cited by 80 · see citing works
Mapping genetic effects on cellular phenotypes with “cell villages”Preprint
Mitchell, J. M., Nemesh, J. C., Ghosh, S. D., Handsaker, R. E., Mello, C. J., Meyer, D., Raghunathan, K., de Rivera, H., Tegtmeyer, M., Hawes, D., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.06.29.174383 · Cited by 81 · see citing works
Self-citationImmunological aspects of RPE cell transplantation
Sugita, S., Mandai, M., Kamao, H., & Takahashi, M. (2021) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2021.100950 · Cited by 77 · see citing works
Context-aware synthetic biology by controller design: Engineering the mammalian cell
Shakiba, N., Jones, R. D., Weiss, R., & Vecchio, D. D. (2021) · Cell Systems · doi:10.1016/j.cels.2021.05.011 · Cited by 77 · see citing works
Huang, M., Tailor, J. K., Zhen, Q., Gillmor, A. H., Miller, M. L., Weishaupt, H., Chen, J., Zheng, T., Nash, E. K., McHenry, L. K., et al. (2019) · Cell stem cell · doi:10.1016/j.stem.2019.05.013 · Cited by 75 · see citing works
Functions of p53 in pluripotent stem cells
Fu, X.-M., Wu, S.-H., Li, B., Xu, Y., & Liu, J. (2019) · Protein & Cell · doi:10.1007/s13238-019-00665-x · Cited by 70 · see citing works
Assou, S., Bouckenheimer, J., & De Vos, J. (2018) · Stem Cells · doi:10.1002/stem.2797 · Cited by 74 · see citing works
Price, C. J., Stavish, D., Gokhale, P. J., Stevenson, B., Sargeant, S., Lacey, J., Rodríguez, T. A., & Barbaric, I. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.07.019 · Cited by 77 · see citing works
Human pallial MGE-type GABAergic interneuron cell therapy for chronic focal epilepsy
Bershteyn, M., Bröer, S., Parekh, M. B., Maury, Y., Havlicek, S., Kriks, S., Fuentealba, L. C., Lee, S., Zhou, R., Subramanyam, G., et al. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.08.013 · Cited by 75 · see citing works
Pluripotent Stem Cells in Developmental Toxicity Testing: A Review of Methodological Advances
Luz, A. L., & Tokar, E. J. (2018) · Toxicological Sciences · doi:10.1093/toxsci/kfy174 · Cited by 74 · see citing works
Kim, M., Rhee, J., Choi, H., Kwon, A., Kim, J., Lee, D., Jekarl, D. W., Lee, S., Kim, Y., & Kim, T. (2017) · Scientific Reports · doi:10.1038/s41598-017-15155-5 · Cited by 75 · see citing works
Tracing the transitions from pluripotency to germ cell fate with CRISPR screening
Hackett, J. A., Huang, Y., Günesdogan, U., Gretarsson, K. H., Kobayashi, T., & Surani, M. A. (2018) · Nature Communications · doi:10.1038/s41467-018-06230-0 · Cited by 68 · see citing works
Genome-Scale CRISPR Screens Identify Human Pluripotency-Specific Genes
Ihry, R. J., Salick, M. R., Ho, D. J., Sondey, M., Kommineni, S., Paula, S., Raymond, J., Henry, B., Frias, E., Wang, Q., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.03.043 · Cited by 71 · see citing works
Jha, B. S., Farnoodian, M., & Bharti, K. (2020) · Stem Cells Translational Medicine · doi:10.1002/sctm.20-0242 · Cited by 73 · see citing works
Chimeric antigen receptor-based natural killer cell immunotherapy in cancer: from bench to bedside
Zhang, B., Yang, M., Zhang, W., Liu, N., Wang, D., Jing, L., Xu, N., Yang, N., & Ren, T. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06438-7 · Cited by 73 · see citing works
Ford, E., Pearlman, J., Ruan, T., Manion, J., Waller, M. A., Neely, G. G., & Caron, L. (2020) · Cells · doi:10.3390/cells9112517 · Cited by 70 · see citing works
Scarless Genome Editing of Human Pluripotent Stem Cells via Transient Puromycin Selection
Steyer, B., Bu, Q., Cory, E., Jiang, K., Duong, S., Sinha, D., Steltzer, S. S., Gamm, D. M., Chang, Q., & Saha, K. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.12.004 · Cited by 64 · see citing works
Challenges Facing Airway Epithelial Cell-Based Therapy for Cystic Fibrosis
Berical, A. C., Lee, R. E., Randell, S. H., & Hawkins, F. J. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00074 · Cited by 61 · see citing works
Goswami, D., Domingo‐Lopez, D. A., Ward, N. A., Millman, J. R., Duffy, G. P., Dolan, E. B., & Roche, E. T. (2021) · Advanced Science · doi:10.1002/advs.202100820 · Cited by 68 · see citing works
Oncogenic PIK3CA promotes cellular stemness in an allele dose-dependent manner
Madsen, R. R., Knox, R. G., Pearce, W. P., López, S., Mahler-Araujo, B. M., McGranahan, N., Vanhaesebroeck, B., & Semple, R. K. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1821093116 · Cited by 67 · see citing works
Clinical-Grade Human Pluripotent Stem Cells for Cell Therapy: Characterization Strategy
Řeháková, D., Souralová, T., & Koutná, I. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21072435 · Cited by 66 · see citing works
Therapeutic Editing of the TP53 Gene: Is CRISPR/Cas9 an Option?
Mirgayazova, R., Khadiullina, R., Chasov, V. V., Mingaleeva, R. N., Рифкатовна, М. Р., Rizvanov, A. A., & Bulatov, E. (2020) · Genes · doi:10.3390/genes11060704 · Cited by 66 · see citing works
Madrid, M., Lakshmipathy, U., Zhang, X., Bharti, K., Wall, D. M., Sato, Y., Muschler, G. F., Ting, A. E., Smith, N., Deguchi, S., et al. (2024) · Cytotherapy · doi:10.1016/j.jcyt.2024.05.022 · Cited by 67 · see citing works
Huang, Z., Powell, R., Phillips, J. B., & Haastert‐Talini, K. (2020) · Cells · doi:10.3390/cells9112497 · Cited by 63 · see citing works
Liquid biopsy in pancreatic cancer: the beginning of a new era
Yadav, D. K., Bai, X., Yadav, R. K., Singh, A., Li, G., Ma, T., Chen, W., & Liang, T. (2018) · Oncotarget · doi:10.18632/oncotarget.24809 · Cited by 60 · see citing works
Yasuda, S.-Y., Ikeda, T., Shahsavarani, H., Yoshida, N., Nayer, B., Hino, M., Vartak-Sharma, N., Suemori, H., & Hasegawa, K. (2018) · Nature Biomedical Engineering · doi:10.1038/s41551-018-0200-7 · Cited by 59 · see citing works
Prentice, D. A. (2019) · Circulation Research · doi:10.1161/circresaha.118.313664 · Cited by 60 · see citing works
- Authors
- Merkle, F. T., Ghosh, S., Kamitaki, N., Mitchell, J., Avior, Y., Mello, C., Kashin, S., Mekhoubad, S., Ilic, D., Charlton, M., Saphier, G., Handsaker, R. E., Genovese, G., Bar, S., Benvenisty, N., McCarroll, S. A., & Eggan, K.
- Affiliations
- Broad Institute (US)
- Hebrew University of Jerusalem (IL)
- Harvard University (US)
- Corresponding author
- McCarroll, Steven A.
- Eggan, Kevin
- ORCID
- Venue
- Nature
- Published
- 2017-04-26
- Volume
- 545
- Issue
- 7653
- Pages
- 229-233
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5427175
- OpenAlex
- W2608500349
- Cited by
- 506
- References
- 44
- Citations by year
- 2026: 38 · 2025: 44 · 2024: 50 · 2023: 42 · 2022: 56 · 2021: 68 · 2020: 65 · 2019: 54 · 2018: 50 · 2017: 35 · 2016: 1
- FWCI
- 22.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Wellcome Trust
- Academy of Medical Sciences (SBF001\1016)
- Rosetrees Trust (M108-F1)
- National Institutes of Health (5K99NS08371)
- Medical Research Council (MC_PC_12009, MR/P501967/1)
- National Heart, Lung, and Blood Institute (R01HL109525)
- National Human Genome Research Institute (R01HG006855)
- National Institute of General Medical Sciences (P01GM099117)
- National Institute of Neurological Disorders and Stroke (K99NS083713)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- human pluripotent stem cells, human embryonic stem cells, induced pluripotent stem cells, TP53 mutation, dominant-negative p53, somatic mosaicism, copy number variation, clonal expansion, tumour suppressor, DNA-binding domain, stem cell culture conditions, exome sequencing, RNA sequencing
- MeSH terms
- Human Embryonic Stem Cells, Protein Domains, Alleles, Cell Count, Cell Differentiation, Cell Division, Cell Line, DNA, DNA Mutational Analysis, Genes, Dominant, Humans, Mosaicism, Mutation, Neoplasms, Selection, Genetic, Genes, p53, Tumor Suppressor Protein p53, Loss of Heterozygosity, Induced Pluripotent Stem Cells, Exome
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