{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T04:27:16Z","timestamp":1768883236632,"version":"3.49.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2023,1,28]],"date-time":"2023-01-28T00:00:00Z","timestamp":1674864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,1,28]],"date-time":"2023-01-28T00:00:00Z","timestamp":1674864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100019687","name":"Hamad bin Khalifa University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100019687","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Rev and Rep"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The multipotent pancreatic progenitor cells (MPCs) co-expressing the transcription factors, PDX1 and NKX6.1, are the source of functional pancreatic \u03b2-cells. The aim of this study was to examine the effect of p53 inhibition in MPCs on the generation of PDX1<jats:sup>+<\/jats:sup>\/NKX6.1<jats:sup>+<\/jats:sup> MPCs and pancreatic \u03b2-cell generation. Human embryonic stem cells (hESCs) were differentiated into MPCs and \u03b2-cells. hESC-MPCs (stage 4) were treated with different concentrations of p53 inhibitors, and their effect was evaluated using different approaches. NKX6.1 was overexpressed during MPCs specification. Inhibition of p53 using pifithrin-\u03bc (PFT-\u03bc) at the MPC stage resulted in a significant increase in the number of PDX1<jats:sup>+<\/jats:sup>\/NKX6.1<jats:sup>+<\/jats:sup> cells and a reduction in the number of CHGA<jats:sup>+<\/jats:sup>\/NKX6.1<jats:sup>\u2212<\/jats:sup> cells. Further differentiation of MPCs treated with PFT-\u03bc into pancreatic \u03b2-cells showed that PFT-\u03bc treatment did not significantly change the number of C-Peptide+ cells; however, the number of C-PEP+ cells co-expressing glucagon (polyhormonal) was significantly reduced in the PFT-\u03bc treated cells. Interestingly, overexpression of NKX6.1 in hESC-MPCs enhanced the expression of key MPC genes and dramatically suppressed p53 expression. Our findings demonstrated that the p53 inhibition during stage 4 of differentiation enhanced MPC generation, prevented premature endocrine induction and favored the differentiation into monohormonal \u03b2-cells. These findings suggest that adding a p53 inhibitor to the differentiation media can significantly enhance the generation of monohormonal \u03b2-cells.<\/jats:p>\n                <jats:p><jats:bold>Graphical Abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s12015-023-10509-1","type":"journal-article","created":{"date-parts":[[2023,1,28]],"date-time":"2023-01-28T05:17:39Z","timestamp":1674883059000},"page":"942-952","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["p53 Inhibition in Pancreatic Progenitors Enhances the Differentiation of Human Pluripotent Stem Cells into Pancreatic \u03b2-Cells"],"prefix":"10.1007","volume":"19","author":[{"given":"Idil I.","family":"Aigha","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7764-6772","authenticated-orcid":false,"given":"Essam M.","family":"Abdelalim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,1,28]]},"reference":[{"key":"10509_CR1","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/S0140-6736(13)60591-7","volume":"383","author":"MA Atkinson","year":"2014","unstructured":"Atkinson, M. A., Eisenbarth, G. S., & Michels, A. W. (2014). Type 1 diabetes. Lancet, 383, 69\u201382.","journal-title":"Lancet"},{"issue":"Suppl 3","key":"10509_CR2","doi-asserted-by":"publisher","first-page":"S16","DOI":"10.2337\/diabetes.53.suppl_3.S16","volume":"53","author":"GC Weir","year":"2004","unstructured":"Weir, G. C., & Bonner-Weir, S. (2004). Five stages of evolving beta-cell dysfunction during progression to diabetes. Diabetes, 53(Suppl 3), S16\u2013S21.","journal-title":"Diabetes"},{"key":"10509_CR3","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.2337\/diab.46.12.1983","volume":"46","author":"R Alejandro","year":"1997","unstructured":"Alejandro, R., Lehmann, R., Ricordi, C., Kenyon, N. S., Angelico, M. C., Burke, G., Esquenazi, V., Nery, J., Betancourt, A. E., Kong, S. S., Miller, J., & Mintz, D. H. (1997). Long-term function (6 years) of islet allografts in type 1 diabetes. Diabetes, 46, 1983\u20131989.","journal-title":"Diabetes"},{"key":"10509_CR4","doi-asserted-by":"publisher","first-page":"710","DOI":"10.2337\/diabetes.50.4.710","volume":"50","author":"EA Ryan","year":"2001","unstructured":"Ryan, E. A., Lakey, J. R., Rajotte, R. V., Korbutt, G. S., Kin, T., Imes, S., Rabinovitch, A., Elliott, J. F., Bigam, D., Kneteman, N. M., Warnock, G. L., Larsen, I., & Shapiro, A. M. (2001). Clinical outcomes and insulin secretion after islet transplantation with the Edmonton protocol. Diabetes, 50, 710\u2013719.","journal-title":"Diabetes"},{"key":"10509_CR5","doi-asserted-by":"publisher","first-page":"515","DOI":"10.2337\/diab.39.4.515","volume":"39","author":"DW Scharp","year":"1990","unstructured":"Scharp, D. W., Lacy, P. E., Santiago, J. V., McCullough, C. S., Weide, L. G., Falqui, L., Marchetti, P., Gingerich, R. L., Jaffe, A. S., Cryer, P. E., et al. (1990). Insulin independence after islet transplantation into type I diabetic patient. Diabetes, 39, 515\u2013518.","journal-title":"Diabetes"},{"key":"10509_CR6","doi-asserted-by":"publisher","first-page":"2494","DOI":"10.1007\/s00125-011-2243-0","volume":"54","author":"RF Gibly","year":"2011","unstructured":"Gibly, R. F., Graham, J. G., Luo, X., Lowe Jr., W. L., Hering, B. J., & Shea, L. D. (2011). Advancing islet transplantation: From engraftment to the immune response. Diabetologia, 54, 2494\u20132505.","journal-title":"Diabetologia"},{"key":"10509_CR7","doi-asserted-by":"publisher","first-page":"2459","DOI":"10.1007\/s00018-020-03710-9","volume":"78","author":"EM Abdelalim","year":"2021","unstructured":"Abdelalim, E. M. (2021). Modeling different types of diabetes using human pluripotent stem cells. Cellular and Molecular Life Sciences, 78, 2459\u20132483.","journal-title":"Cellular and Molecular Life Sciences"},{"key":"10509_CR8","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1007\/s12015-014-9503-6","volume":"10","author":"EM Abdelalim","year":"2014","unstructured":"Abdelalim, E. M., Bonnefond, A., Bennaceur-Griscelli, A., & Froguel, P. (2014). Pluripotent stem cells as a potential tool for disease modelling and cell therapy in diabetes. Stem Cell Reviews and Reports, 10, 327\u2013337.","journal-title":"Stem Cell Reviews and Reports"},{"key":"10509_CR9","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1007\/s12015-017-9783-8","volume":"14","author":"D Ribeiro","year":"2018","unstructured":"Ribeiro, D., Kvist, A. J., Wittung-Stafshede, P., Hicks, R., & Forslow, A. (2018). 3D-models of insulin-producing beta-cells: From primary islet cells to stem cell-derived islets. Stem Cell Reviews and Reports, 14, 177\u2013188.","journal-title":"Stem Cell Reviews and Reports"},{"key":"10509_CR10","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1111\/brv.12349","volume":"93","author":"S Al-Khawaga","year":"2018","unstructured":"Al-Khawaga, S., Memon, B., Butler, A. E., Taheri, S., Abou-Samra, A. B., & Abdelalim, E. M. (2018). Pathways governing development of stem cell-derived pancreatic beta cells: Lessons from embryogenesis. Biological Reviews of the Cambridge Philosophical Society, 93, 364\u2013389.","journal-title":"Biological Reviews of the Cambridge Philosophical Society"},{"key":"10509_CR11","doi-asserted-by":"publisher","first-page":"2683","DOI":"10.1007\/s12015-022-10391-3","volume":"18","author":"K Verhoeff","year":"2022","unstructured":"Verhoeff, K., Cuesta-Gomez, N., Jasra, I., Marfil-Garza, B., Dadheech, N., & Shapiro, A. M. J. (2022). Optimizing generation of stem cell-derived islet cells. Stem Cell Reviews and Reports, 18, 2683\u20132698.","journal-title":"Stem Cell Reviews and Reports"},{"key":"10509_CR12","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1038\/s41586-019-1168-5","volume":"569","author":"A Veres","year":"2019","unstructured":"Veres, A., Faust, A. L., Bushnell, H. L., Engquist, E. N., Kenty, J. H., Harb, G., Poh, Y. C., Sintov, E., Gurtler, M., Pagliuca, F. W., Peterson, Q. P., & Melton, D. A. (2019). Charting cellular identity during human in vitro beta-cell differentiation. Nature, 569, 368\u2013373.","journal-title":"Nature"},{"key":"10509_CR13","doi-asserted-by":"publisher","first-page":"e1003274","DOI":"10.1371\/journal.pgen.1003274","volume":"9","author":"AE Schaffer","year":"2013","unstructured":"Schaffer, A. E., Taylor, B. L., Benthuysen, J. R., Liu, J., Thorel, F., Yuan, W., Jiao, Y., Kaestner, K. H., Herrera, P. L., Magnuson, M. A., May, C. L., & Sander, M. (2013). Nkx6.1 controls a gene regulatory network required for establishing and maintaining pancreatic Beta cell identity. PLoS Genetics, 9, e1003274.","journal-title":"PLoS Genetics"},{"key":"10509_CR14","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1172\/JCI200316537","volume":"111","author":"JD Johnson","year":"2003","unstructured":"Johnson, J. D., Ahmed, N. T., Luciani, D. S., Han, Z., Tran, H., Fujita, J., Misler, S., Edlund, H., & Polonsky, K. S. (2003). Increased islet apoptosis in Pdx1+\/\u2212 mice. The Journal of Clinical Investigation, 111, 1147\u20131160.","journal-title":"The Journal of Clinical Investigation"},{"key":"10509_CR15","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.15252\/embj.201591058","volume":"34","author":"HA Russ","year":"2015","unstructured":"Russ, H. A., Parent, A. V., Ringler, J. J., Hennings, T. G., Nair, G. G., Shveygert, M., Guo, T., Puri, S., Haataja, L., Cirulli, V., Blelloch, R., Szot, G. L., Arvan, P., & Hebrok, M. (2015). Controlled induction of human pancreatic progenitors produces functional beta-like cells in vitro. The EMBO Journal, 34, 1759\u20131772.","journal-title":"The EMBO Journal"},{"key":"10509_CR16","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1016\/j.cell.2014.09.040","volume":"159","author":"FW Pagliuca","year":"2014","unstructured":"Pagliuca, F. W., Millman, J. R., Gurtler, M., Segel, M., Van Dervort, A., Ryu, J. H., Peterson, Q. P., Greiner, D., & Melton, D. A. (2014). Generation of functional human pancreatic beta cells in vitro. Cell, 159, 428\u2013439.","journal-title":"Cell"},{"key":"10509_CR17","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1038\/nbt.3033","volume":"32","author":"A Rezania","year":"2014","unstructured":"Rezania, A., Bruin, J. E., Arora, P., Rubin, A., Batushansky, I., Asadi, A., O'Dwyer, S., Quiskamp, N., Mojibian, M., Albrecht, T., Yang, Y. H., Johnson, J. D., & Kieffer, T. J. (2014). Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nature Biotechnology, 32, 1121\u20131133.","journal-title":"Nature Biotechnology"},{"key":"10509_CR18","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1186\/s13287-020-01977-0","volume":"11","author":"II Aigha","year":"2020","unstructured":"Aigha, I. I., & Abdelalim, E. M. (2020). NKX6.1 transcription factor: A crucial regulator of pancreatic beta cell development, identity, and proliferation. Stem Cell Research & Therapy, 11, 459.","journal-title":"Stem Cell Research & Therapy"},{"key":"10509_CR19","doi-asserted-by":"publisher","first-page":"25134","DOI":"10.1074\/jbc.M513901200","volume":"281","author":"KB Spurgers","year":"2006","unstructured":"Spurgers, K. B., Gold, D. L., Coombes, K. R., Bohnenstiehl, N. L., Mullins, B., Meyn, R. E., Logothetis, C. J., & McDonnell, T. J. (2006). Identification of cell cycle regulatory genes as principal targets of p53-mediated transcriptional repression. The Journal of Biological Chemistry, 281, 25134\u201325142.","journal-title":"The Journal of Biological Chemistry"},{"key":"10509_CR20","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s13287-017-0759-z","volume":"9","author":"B Memon","year":"2018","unstructured":"Memon, B., Karam, M., Al-Khawaga, S., & Abdelalim, E. M. (2018). Enhanced differentiation of human pluripotent stem cells into pancreatic progenitors co-expressing PDX1 and NKX6.1. Stem Cell Research & Therapy, 9, 15.","journal-title":"Stem Cell Research & Therapy"},{"key":"10509_CR21","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1007\/7651_2020_323","volume":"2454","author":"B Memon","year":"2022","unstructured":"Memon, B., & Abdelalim, E. M. (2022). Highly efficient differentiation of human pluripotent stem cells into pancreatic progenitors co-expressing PDX1 and NKX6.1. Methods in Molecular Biology, 2454, 351\u2013363.","journal-title":"Methods in Molecular Biology"},{"key":"10509_CR22","doi-asserted-by":"publisher","unstructured":"Memon, B., & Abdelalim, E. M. (2021). Differentiation of human pluripotent stem cells into pancreatic beta-cell precursors in a 2D culture system. Journal of Visualized Experiments, (178).  https:\/\/doi.org\/10.3791\/63298","DOI":"10.3791\/63298"},{"key":"10509_CR23","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.1126\/science.285.5434.1733","volume":"285","author":"PG Komarov","year":"1999","unstructured":"Komarov, P. G., Komarova, E. A., Kondratov, R. V., Christov-Tselkov, K., Coon, J. S., Chernov, M. V., & Gudkov, A. V. (1999). A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science, 285, 1733\u20131737.","journal-title":"Science"},{"key":"10509_CR24","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1016\/j.bbrc.2005.03.153","volume":"331","author":"AV Gudkov","year":"2005","unstructured":"Gudkov, A. V., & Komarova, E. A. (2005). Prospective therapeutic applications of p53 inhibitors. Biochemical and Biophysical Research Communications, 331, 726\u2013736.","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"10509_CR25","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1038\/nchembio809","volume":"2","author":"E Strom","year":"2006","unstructured":"Strom, E., Sathe, S., Komarov, P. G., Chernova, O. B., Pavlovska, I., Shyshynova, I., Bosykh, D. A., Burdelya, L. G., Macklis, R. M., Skaliter, R., Komarova, E. A., & Gudkov, A. V. (2006). Small-molecule inhibitor of p53 binding to mitochondria protects mice from gamma radiation. Nature Chemical Biology, 2, 474\u2013479.","journal-title":"Nature Chemical Biology"},{"key":"10509_CR26","doi-asserted-by":"publisher","first-page":"3752","DOI":"10.1101\/gad.12.23.3752","volume":"12","author":"A Krapp","year":"1998","unstructured":"Krapp, A., Knofler, M., Ledermann, B., Burki, K., Berney, C., Zoerkler, N., Hagenbuchle, O., & Wellauer, P. K. (1998). The bHLH protein PTF1-p48 is essential for the formation of the exocrine and the correct spatial organization of the endocrine pancreas. Genes & Development, 12, 3752\u20133763.","journal-title":"Genes & Development"},{"key":"10509_CR27","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1093\/stcltm\/szac030","volume":"11","author":"B Memon","year":"2022","unstructured":"Memon, B., & Abdelalim, E. M. (2022). Toward precision medicine with human pluripotent stem cells for diabetes. Stem Cells Translational Medicine, 11, 704\u2013714.","journal-title":"Stem Cells Translational Medicine"},{"key":"10509_CR28","doi-asserted-by":"publisher","first-page":"2395","DOI":"10.1016\/j.stemcr.2021.07.021","volume":"16","author":"Y Jiang","year":"2021","unstructured":"Jiang, Y., Chen, C., Randolph, L. N., Ye, S., Zhang, X., Bao, X., & Lian, X. L. (2021). Generation of pancreatic progenitors from human pluripotent stem cells by small molecules. Stem Cell Reports, 16, 2395\u20132409.","journal-title":"Stem Cell Reports"},{"key":"10509_CR29","doi-asserted-by":"publisher","unstructured":"Jain, A. K., & Barton, M. C. (2018). p53: Emerging roles in stem cells, development and beyond. Development, 145(8), dev158360.  https:\/\/doi.org\/10.1242\/dev.158360","DOI":"10.1242\/dev.158360"},{"key":"10509_CR30","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1038\/nm.3862","volume":"21","author":"BF Belgardt","year":"2015","unstructured":"Belgardt, B. F., Ahmed, K., Spranger, M., Latreille, M., Denzler, R., Kondratiuk, N., von Meyenn, F., Villena, F. N., Herrmanns, K., Bosco, D., Kerr-Conte, J., Pattou, F., Rulicke, T., & Stoffel, M. (2015). The microRNA-200 family regulates pancreatic beta cell survival in type 2 diabetes. Nature Medicine, 21, 619\u2013627.","journal-title":"Nature Medicine"},{"key":"10509_CR31","doi-asserted-by":"publisher","first-page":"101650","DOI":"10.1016\/j.molmet.2022.101650","volume":"67","author":"C Uhlemeyer","year":"2022","unstructured":"Uhlemeyer, C., Muller, N., Rieck, M., Kuboth, J., Schlegel, C., Griess, K., Dorweiler, T. F., Heiduschka, S., Eckel, J., Roden, M., Lammert, E., Stoffel, M., & Belgardt, B. F. (2022). Selective ablation of P53 in pancreatic beta cells fails to ameliorate glucose metabolism in genetic, dietary and pharmacological models of diabetes mellitus. Molecular Metabolism, 67, 101650.","journal-title":"Molecular Metabolism"},{"key":"10509_CR32","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.cmet.2013.11.007","volume":"19","author":"S Tornovsky-Babeay","year":"2014","unstructured":"Tornovsky-Babeay, S., Dadon, D., Ziv, O., Tzipilevich, E., Kadosh, T., Schyr-Ben Haroush, R., Hija, A., Stolovich-Rain, M., Furth-Lavi, J., Granot, Z., Porat, S., Philipson, L. H., Herold, K. C., Bhatti, T. R., Stanley, C., Ashcroft, F. M., In't Veld, P., Saada, A., Magnuson, M. A., et al. (2014). Type 2 diabetes and congenital hyperinsulinism cause DNA double-strand breaks and p53 activity in beta cells. Cell Metabolism, 19, 109\u2013121.","journal-title":"Cell Metabolism"},{"key":"10509_CR33","doi-asserted-by":"publisher","first-page":"3116","DOI":"10.1073\/pnas.1318951111","volume":"111","author":"A Hoshino","year":"2014","unstructured":"Hoshino, A., Ariyoshi, M., Okawa, Y., Kaimoto, S., Uchihashi, M., Fukai, K., Iwai-Kanai, E., Ikeda, K., Ueyama, T., Ogata, T., & Matoba, S. (2014). Inhibition of p53 preserves Parkin-mediated mitophagy and pancreatic beta-cell function in diabetes. Proceedings of the National Academy of Sciences of the United States of America, 111, 3116\u20133121.","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10509_CR34","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1101\/gad.207001.112","volume":"27","author":"S Georgia","year":"2013","unstructured":"Georgia, S., Kanji, M., & Bhushan, A. (2013). DNMT1 represses p53 to maintain progenitor cell survival during pancreatic organogenesis. Genes & Development, 27, 372\u2013377.","journal-title":"Genes & Development"},{"key":"10509_CR35","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1007\/s12015-020-10018-5","volume":"16","author":"MH Maloy","year":"2020","unstructured":"Maloy, M. H., Ferrer, M. A., & Parashurama, N. (2020). In vivo differentiation of stem cell-derived human pancreatic progenitors to treat type 1 diabetes. Stem Cell Reviews and Reports, 16, 1139\u20131155.","journal-title":"Stem Cell Reviews and Reports"},{"key":"10509_CR36","doi-asserted-by":"publisher","first-page":"7297","DOI":"10.1073\/pnas.0502168102","volume":"102","author":"JC Schisler","year":"2005","unstructured":"Schisler, J. C., Jensen, P. B., Taylor, D. G., Becker, T. C., Knop, F. K., Takekawa, S., German, M., Weir, G. C., Lu, D., Mirmira, R. G., & Newgard, C. B. (2005). The Nkx6.1 homeodomain transcription factor suppresses glucagon expression and regulates glucose-stimulated insulin secretion in islet beta cells. Proceedings of the National Academy of Sciences of the United States of America, 102, 7297\u20137302.","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10509_CR37","doi-asserted-by":"publisher","first-page":"3465","DOI":"10.1128\/MCB.01791-07","volume":"28","author":"JC Schisler","year":"2008","unstructured":"Schisler, J. C., Fueger, P. T., Babu, D. A., Hohmeier, H. E., Tessem, J. S., Lu, D., Becker, T. C., Naziruddin, B., Levy, M., Mirmira, R. G., & Newgard, C. B. (2008). Stimulation of human and rat islet beta-cell proliferation with retention of function by the homeodomain transcription factor Nkx6.1. Molecular and Cellular Biology, 28, 3465\u20133476.","journal-title":"Molecular and Cellular Biology"},{"key":"10509_CR38","first-page":"6","volume-title":"Genome stability requires p53","author":"CM Eischen","year":"2016","unstructured":"Eischen, C. M. (2016). Genome stability requires p53 (p. 6). Cold Spring Harb Perspect Med."},{"key":"10509_CR39","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/ncb1211","volume":"7","author":"T Lin","year":"2005","unstructured":"Lin, T., Chao, C., Saito, S., Mazur, S. J., Murphy, M. E., Appella, E., & Xu, Y. (2005). p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression. Nature Cell Biology, 7, 165\u2013171.","journal-title":"Nature Cell Biology"},{"key":"10509_CR40","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.bbrc.2012.03.041","volume":"420","author":"EM Abdelalim","year":"2012","unstructured":"Abdelalim, E. M., & Tooyama, I. (2012). The p53 inhibitor, pifithrin-alpha, suppresses self-renewal of embryonic stem cells. Biochemical and Biophysical Research Communications, 420, 605\u2013610.","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"10509_CR41","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1016\/j.bbrc.2013.12.030","volume":"443","author":"EM Abdelalim","year":"2014","unstructured":"Abdelalim, E. M., & Tooyama, I. (2014). Knockdown of p53 suppresses Nanog expression in embryonic stem cells. Biochemical and Biophysical Research Communications, 443, 652\u2013657.","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"10509_CR42","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1002\/stem.1925","volume":"33","author":"Y He","year":"2015","unstructured":"He, Y., de Castro, L. F., Shin, M. H., Dubois, W., Yang, H. H., Jiang, S., Mishra, P. J., Ren, L., Gou, H., Lal, A., Khanna, C., Merlino, G., Lee, M., Robey, P. G., & Huang, J. (2015). p53 loss increases the osteogenic differentiation of bone marrow stromal cells. Stem Cells, 33, 1304\u20131319.","journal-title":"Stem Cells"},{"key":"10509_CR43","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1083\/jcb.200508130","volume":"172","author":"CJ Lengner","year":"2006","unstructured":"Lengner, C. J., Steinman, H. A., Gagnon, J., Smith, T. W., Henderson, J. E., Kream, B. E., Stein, G. S., Lian, J. B., & Jones, S. N. (2006). Osteoblast differentiation and skeletal development are regulated by Mdm2-p53 signaling. The Journal of Cell Biology, 172, 909\u2013921.","journal-title":"The Journal of Cell Biology"},{"key":"10509_CR44","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1083\/jcb.200507106","volume":"172","author":"X Wang","year":"2006","unstructured":"Wang, X., Kua, H. Y., Hu, Y., Guo, K., Zeng, Q., Wu, Q., Ng, H. H., Karsenty, G., de Crombrugghe, B., Yeh, J., & Li, B. (2006). p53 functions as a negative regulator of osteoblastogenesis, osteoblast-dependent osteoclastogenesis, and bone remodeling. The Journal of Cell Biology, 172, 115\u2013125.","journal-title":"The Journal of Cell Biology"},{"issue":"Pt 6","key":"10509_CR45","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1242\/jcs.109.6.1509","volume":"109","author":"A Ferreira","year":"1996","unstructured":"Ferreira, A., & Kosik, K. S. (1996). Accelerated neuronal differentiation induced by p53 suppression. Journal of Cell Science, 109(Pt 6), 1509\u20131516.","journal-title":"Journal of Cell Science"},{"key":"10509_CR46","doi-asserted-by":"publisher","first-page":"e737","DOI":"10.1038\/cddis.2013.246","volume":"4","author":"Y Hadjal","year":"2013","unstructured":"Hadjal, Y., Hadadeh, O., Yazidi, C. E., Barruet, E., & Binetruy, B. (2013). A p38MAPK-p53 cascade regulates mesodermal differentiation and neurogenesis of embryonic stem cells. Cell Death & Disease, 4, e737.","journal-title":"Cell Death & Disease"},{"key":"10509_CR47","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1016\/j.celrep.2014.10.012","volume":"9","author":"A Freije","year":"2014","unstructured":"Freije, A., Molinuevo, R., Ceballos, L., Cagigas, M., Alonso-Lecue, P., Rodriguez, R., Menendez, P., Aberdam, D., De Diego, E., & Gandarillas, A. (2014). Inactivation of p53 in human keratinocytes leads to squamous differentiation and shedding via replication stress and mitotic slippage. Cell Reports, 9, 1349\u20131360.","journal-title":"Cell Reports"},{"key":"10509_CR48","doi-asserted-by":"publisher","first-page":"e019365","DOI":"10.1161\/JAHA.120.019365","volume":"10","author":"N Kundu","year":"2021","unstructured":"Kundu, N., Nandula, S. R., Asico, L. D., Fakhri, M., Banerjee, J., Jose, P. A., & Sen, S. (2021). Transplantation of apoptosis-resistant endothelial progenitor cells improves renal function in diabetic kidney disease. Journal of the American Heart Association, 10, e019365.","journal-title":"Journal of the American Heart Association"},{"key":"10509_CR49","doi-asserted-by":"publisher","first-page":"E391","DOI":"10.1152\/ajpendo.00073.2017","volume":"313","author":"H Li","year":"2017","unstructured":"Li, H., Liu, J., Wang, Y., Fu, Z., Huttemann, M., Monks, T. J., Chen, A. F., & Wang, J. M. (2017). MiR-27b augments bone marrow progenitor cell survival via suppressing the mitochondrial apoptotic pathway in type 2 diabetes. American Journal of Physiology. Endocrinology and Metabolism, 313, E391\u2013E401.","journal-title":"American Journal of Physiology. Endocrinology and Metabolism"},{"key":"10509_CR50","doi-asserted-by":"publisher","first-page":"2916","DOI":"10.1002\/stem.2471","volume":"34","author":"JBT Moore","year":"2016","unstructured":"Moore, J. B. T., Zhao, J., Keith, M. C., Amraotkar, A. R., Wysoczynski, M., Hong, K. U., & Bolli, R. (2016). The epigenetic regulator HDAC1 modulates transcription of a Core cardiogenic program in human cardiac mesenchymal stromal cells through a p53-dependent mechanism. Stem Cells, 34, 2916\u20132929.","journal-title":"Stem Cells"}],"container-title":["Stem Cell Reviews and Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12015-023-10509-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12015-023-10509-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12015-023-10509-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T14:35:03Z","timestamp":1684161303000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12015-023-10509-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,28]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,5]]}},"alternative-id":["10509"],"URL":"https:\/\/doi.org\/10.1007\/s12015-023-10509-1","relation":{},"ISSN":["2629-3269","2629-3277"],"issn-type":[{"value":"2629-3269","type":"print"},{"value":"2629-3277","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,28]]},"assertion":[{"value":"16 January 2023","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2023","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Notapplicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publications"}},{"value":"The authors declare no competing interests in this manuscript.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}