Functions of p53 in pluripotent stem cells

doi:10.1007/s13238-019-00665-x

Protein Cell

2020, Vol. 11

Issue (1) : 71-78 https://doi.org/10.1007/s13238-019-00665-x

REVIEW

Functions of p53 in pluripotent stem cells

Xuemei Fu¹(

), Shouhai Wu², Bo Li³, Yang Xu¹, Jingfeng Liu⁴

¹. The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China
². Center for Regenerative and Translational Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510632, China
³. Department of Biochemistry and Molecular Biology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
⁴. Cancer Research Institute, Guangdong Provincial Key Laboratory of Tumor Immunotherapy, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China

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Abstract

Pluripotent stem cells (PSCs) are capable of unlimited self-renewal in culture and differentiation into all functional cell types in the body, and thus hold great promise for regenerative medicine. To achieve their clinical potential, it is critical for PSCs to maintain genomic stability during the extended proliferation. The critical tumor suppressor p53 is required to maintain genomic stability of mammalian cells. In response to DNA damage or oncogenic stress, p53 plays multiple roles in maintaining genomic stability of somatic cells by inducing cell cycle arrest, apoptosis, and senescence to prevent the passage of genetic mutations to the daughter cells. p53 is also required to maintain the genomic stability of PSCs. However, in response to the genotoxic stresses, a primary role of p53 in PSCs is to induce the differentiation of PSCs and inhibit pluripotency, providing mechanisms to maintain the genomic stability of the self-renewing PSCs. In addition, the roles of p53 in cellular metabolism might also contribute to genomic stability of PSCs by limiting oxidative stress. In summary, the elucidation of the roles of p53 in PSCs will be a prerequisite for developing safe PSC-based cell therapy.

Keywords p53 embryonic stem cells induced pluripotent stem cells genetic stability metabolism

Corresponding Author(s): Xuemei Fu

Issue Date: 02 March 2020

Cite this article:

Xuemei Fu,Shouhai Wu,Bo Li, et al. Functions of p53 in pluripotent stem cells[J]. Protein Cell, 2020, 11(1): 71-78.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-019-00665-x
https://academic.hep.com.cn/pac/EN/Y2020/V11/I1/71

1	MI Aladjem, BT Spike, LW Rodewald, TJ Hope, M Klemm, R Jaenisch, GM Wahl (1998) ES cells do not activate p53-dependent stress responses and undergo p53-independent apoptosis in response to DNA damage. Curr Biol 8:145–155 https://doi.org/10.1016/S0960-9822(98)70061-2
2	MG Angelos, DS Kaufman (2015) Pluripotent stem cell applications for regenerative medicine. Curr Opin Organ Transplant 20:663–670 https://doi.org/10.1097/MOT.0000000000000244
3	A Banito, ST Rashid, JC Acosta, S Li, CF Pereira, I Geti, S Pinho, JC Silva, V Azuara, M Walshet al. (2009) Senescence impairs successful reprogramming to pluripotent stem cells. Genes Dev 23:2134–2139 https://doi.org/10.1101/gad.1811609
4	NA Barlev, L Liu, NH Chehab, K Mansfield, KG Harris, TD Halazonetis, SL Berger (2001) Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases. Mol Cell 8:1243–1254 https://doi.org/10.1016/S1097-2765(01)00414-2
5	C Blanpain, BD Simons (2013) Unravelling stem cell dynamics by lineage tracing. Nat Rev Mol Cell Biol 14:489–502 https://doi.org/10.1038/nrm3625
6	MJ Boland, JL Hazen, KL Nazor, AR Rodriguez, W Gifford, G, Martin S Kupriyanov, KK Baldwin (2009) Adult mice generated from induced pluripotent stem cells. Nature 461:91–94 https://doi.org/10.1038/nature08310
7	GL Boulting, E Kiskinis, GF Croft, MW Amoroso, DH Oakley, BJ Wainger, DJ Williams, DJ Kahler, M Yamaki, L Davidowet al. (2011) A functionally characterized test set of human induced pluripotent stem cells. Nat Biotechnol 29:279–286 https://doi.org/10.1038/nbt.1783
8	CL Brooks, W Gu (2006) p53 ubiquitination: Mdm2 and beyond. Mol Cell 21:307–315 https://doi.org/10.1016/j.molcel.2006.01.020
9	RB Cervantes, JR Stringer, C Shao, JA Tischfield, PJ Stambrook (2002) Embryonic stem cells and somatic cells differ in mutation frequency and type. Proc Natl Acad Sci USA 99:3586–3590 https://doi.org/10.1073/pnas.062527199
10	C Chao, M Hergenhahn, MD Kaeser, Z Wu, S Saito, R Iggo, M Hollstein, E Appella, Y Xu (2003) Cell type- and promoterspecific roles of Ser18 phosphorylation in regulating p53 responses. J Biol Chem 278:41028–41033 https://doi.org/10.1074/jbc.M306938200
11	C Chao, D Herr, J Chun, Y Xu (2006) Ser18 and 23 phosphorylation is required for p53-dependent apoptosis and tumor suppression. Embo J 25:2615–2622 https://doi.org/10.1038/sj.emboj.7601167
12	Z Chen, T Zhao, Y Xu (2012) The genomic stability of induced pluripotent stem cells. Protein Cell 3:271–277 https://doi.org/10.1007/s13238-012-2922-8
13	TS Cliff, S Dalton (2017) Metabolic switching and cell fate decisions: implications for pluripotency, reprogramming and development. Curr Opin Genet Dev 46:44–49 https://doi.org/10.1016/j.gde.2017.06.008
14	M Coutts, HS Keirstead (2008) Stem cells for the treatment of spinal cord injury. Exp Neurol 209:368–377 https://doi.org/10.1016/j.expneurol.2007.09.002
15	AL Craig, L Burch, B Vojtesek, J Mikutowska, A Thompson, TR Hupp (1999) Novel phosphorylation sites of human tumour suppressor protein p53 at Ser20 and Thr18 that disrupt the binding of mdm2 (mouse double minute 2) protein are modified in human cancers. Biochem J 342:133–141 https://doi.org/10.1042/bj3420133
16	KA D’Amour, AG Bang, S Eliazer, OG Kelly, AD Agulnick, NG, Smart MA Moorman, E Kroon, MK, Carpenter EE Baetge (2006) Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotech 24:1392–1401 https://doi.org/10.1038/nbt1259
17	PE de Almeida, EH Meyer, NG Kooreman, S Diecke, D Dey, V, Sanchez-Freire S Hu, A Ebert, J Odegaard, NM Mordwinkinet al. (2014) Transplanted terminally differentiated induced pluripotent stem cells are accepted by immune mechanisms similar to self-tolerance. Nat Commun 5:3903 https://doi.org/10.1038/ncomms4903
18	T, Deuse X Hu, S Agbor-Enoh, M Koch, MH Spitzer, A Gravina, M Alawi, A Marishta, B, Peters Z Kosaloglu-Yalcin, et al. (2019) De novo mutations in mitochondrial DNA of iPSCs produce immunogenic neoepitopes in mice and humans. Nat Biotechnol 37:1137–1144 https://doi.org/10.1038/s41587-019-0227-7
19	CM Eischen (2016) Genome stability requires p53. Cold Spring Harb Perspect Med 6:a026096 https://doi.org/10.1101/cshperspect.a026096
20	A Fatica, I Bozzoni (2014) Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet 15:7–21 https://doi.org/10.1038/nrg3606
21	L Feng, T Lin, H Uranishi, W Gu, Y Xu (2005) Functional analysis of the roles of posttranslational modifications at the p53 C terminus in regulating p53 stability and activity. Mol Cell Biol 25:5389–5395 https://doi.org/10.1128/MCB.25.13.5389-5395.2005
22	L Feng, M Hollstein, Y Xu (2006) Ser46 phosphorylation regulates p53-dependent apoptosis and replicative senescence. Cell Cycle 5:2812–2819 Epub 2006 Dec 2811 https://doi.org/10.4161/cc.5.23.3526
23	A Giorgetti, N Montserrat, T Aasen, F Gonzalez, I Rodràguez-Pizà , R Vassena, A, Raya S Boué, MJ Barrero, BA Corbellaet al. (2009) Generation of induced pluripotent stem cells from human cord blood using OCT4 and SOX2. Cell Stem Cell 5:353–357 https://doi.org/10.1016/j.stem.2009.09.008
24	A Gore, Z Li, H-L Fung, JE Young, S Agarwal, J Antosiewicz-Bourget, I Canto, A Giorgetti, MA Israel, E Kiskiniset al. (2011) Somatic coding mutations in human induced pluripotent stem cells. Nature 471:63–67 https://doi.org/10.1038/nature09805
25	W Gu, RG Roeder (1997) Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell 90:595–606 https://doi.org/10.1016/S0092-8674(00)80521-8
26	D Hanahan, RA Weinberg (2011) Hallmarks of cancer: the next generation. Cell 144:646–674 https://doi.org/10.1016/j.cell.2011.02.013
27	J, He Z Rong, X Fu, Y Xu (2017) A safety checkpoint to eliminate cancer risk of the immune evasive cells derived from human embryonic stem cells. Stem Cells.2568 https://doi.org/10.1002/stem.2568
28	M Hollstein, D Sidransky, B Vogelstein, CC Harris (1991) p53 mutations in human cancers. Science 253:49–53 https://doi.org/10.1126/science.1905840
29	W Hu, Z Feng, AK Teresky, AJ Levine (2007) p53 regulates maternal reproduction through LIF. Nature 450:721–724 https://doi.org/10.1038/nature05993
30	K Inoue, A Kurabayashi, T Shuin, Y, Ohtsuki M Furihata (2012) Overexpression of p53 protein in human tumors. Med Mol Morphol 45:115–123 https://doi.org/10.1007/s00795-012-0575-6
31	AK Jain, MC Barton (2018) P53: emerging roles in stem cells, development and beyond. Development 145:dev158360 https://doi.org/10.1242/dev.158360
32	AK Jain, K Allton, M Iacovino, E Mahen, RJ Milczarek, TP Zwaka, M Kyba, MC Barton (2012) p53 regulates cell cycle and microRNAs to promote differentiation of human embryonic stem cells. PLoS Biol 10:e1001268 https://doi.org/10.1371/journal.pbio.1001268
33	AK Jain, Y Xi, R, McCarthy K Allton, KC Akdemir, LR Patel, B Aronow, C Lin, W Li, L Yanget al. (2016) LncPRESS1 Is a p53- regulated LncRNA that safeguards pluripotency by disrupting SIRT6-mediated de-acetylation of histone H3K56. Mol Cell 64:967–981 https://doi.org/10.1016/j.molcel.2016.10.039
34	A Janic, LJ Valente, MJ Wakefield, L Di Stefano, L Milla, S Wilcox, H Yang, L Tai, CJ Vandenberg, AJ Kuehet al. (2018) DNA repair processes are critical mediators of p53-dependent tumor suppression. Nat Med 24:947–953 https://doi.org/10.1038/s41591-018-0043-5
35	J Ji, SH Ng, V Sharma, D Neculai, S Hussein, M Sam, Q Trinh, GM Church, JD McPherson, A Nagyet al. (2012) Elevated coding mutation rate during the reprogramming of human somatic cells into induced pluripotent stem cells. Stem Cells 30:435–440 https://doi.org/10.1002/stem.1011
36	J Jiang, W Lv, X Ye, L Wang, M Zhang, H Yang, M Okuka, C Zhou, X Zhang, L Liuet al. (2013) Zscan4 promotes genomic stability during reprogramming and dramatically improves the quality of iPS cells as demonstrated by tetraploid complementation. Cell Res 23:92–106 https://doi.org/10.1038/cr.2012.157
37	T Kawamura, J Suzuki, YV Wang, S Menendez, LB Morera, A Raya, GM Wahl, JCI Belmonte (2009) Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature 460:1140–1144 https://doi.org/10.1038/nature08311
38	JB Kim, H Zaehres, G Wu, L Gentile, K Ko, V Sebastiano, MJ Araúzo-Bravo, D Ruau, DW Han, M Zenkeet al. (2008) Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature 454:646–650 https://doi.org/10.1038/nature07061
39	JB Kim, V Sebastiano, G Wu, MJ Araúzo-Bravo, P Sasse, L Gentile, K Ko, D Ruau, M Ehrich, D van den Boomet al. (2009a) Oct4- induced pluripotency in adult neural stem cells. Cell 136:411–419 https://doi.org/10.1016/j.cell.2009.01.023
40	JV Kim, SS Kang, ML Dustin, DB McGavern (2009b) Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis. Nature 457:191–195 https://doi.org/10.1038/nature07591
41	J Kim, L Yu, W Chen, Y Xu, M Wu, D Todorova, Q Tang, B Feng, L Jiang, J Heet al. (2019) Wild-type p53 promotes cancer metabolic switch by inducing PUMA-dependent suppression of oxidative phosphorylation. Cancer Cell 35(2):191–203 https://doi.org/10.1016/j.ccell.2018.12.012
42	EA Kimbrel, R Lanza (2015) Current status of pluripotent stem cells: moving the first therapies to the clinic. Nat Rev Drug Discov 14:681–692 https://doi.org/10.1038/nrd4738
43	LJ Ko, C Prives (1996) p53: puzzle and paradigm. Genes Dev 10:1054–1072 https://doi.org/10.1101/gad.10.9.1054
44	G Koifman, Y Shetzer, S Eizenberger, H Solomon, R Rotkopf, A Molchadsky, G Lonetto, N Goldfinger, V Rotter (2018) A mutant p53-dependent embryonic stem cell gene signature is associated with augmented tumorigenesis of stem cells. Cancer Res 78:5833 https://doi.org/10.1158/0008-5472.CAN-18-0805
45	E Kroon, LA Martinson, K Kadoya, AG Bang, OG Kelly, S Eliazer, H Young, M Richardson, NG Smart, J Cunninghamet al. (2008) Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotech 26:443–452 https://doi.org/10.1038/nbt1393
46	CF Labuschagne, F Zani, KH Vousden (2018) Control of metabolism by p53: cancer and beyond. Biochim Biophys Acta 1870:32–42 https://doi.org/10.1016/j.bbcan.2018.06.001
47	BB Lake, J Fink, L Klemetsaune, X Fu, JR Jeffers, GP Zambetti, Y Xu (2012) Context-dependent enhancement of induced pluripotent stem cell reprogramming by silencing Puma. Stem cells 30:888–897 https://doi.org/10.1002/stem.1054
48	DP Lane (1992) p53, guardian of the genome. Nature 358:15–16 https://doi.org/10.1038/358015a0
49	D-F Lee, J Su, Y-S Ang, X Carvajal-Vergara, S Mulero-Navarro, F Pereira Carlos, J Gingold, H-L Wang, R Zhao, A Sevillaet al. (2012) Regulation of embryonic and induced pluripotency by aurora kinase-p53 signaling. Cell Stem Cell 11:179–194 https://doi.org/10.1016/j.stem.2012.05.020
50	AJ Levine (1997) p53, the cellular gatekeeper for growth and division. Cell 88:323–331 https://doi.org/10.1016/S0092-8674(00)81871-1
51	W Li, W Wei, S Zhu, J Zhu, Y Shi, T Lin, E Hao, A Hayek, H Deng, S Ding (2009) Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors. Cell Stem Cell 4:16–19 https://doi.org/10.1016/j.stem.2008.11.014
52	M Li, Y He, W Dubois, X Wu, J Shi, J Huang (2012) Distinct regulatory mechanisms and functions for p53-activated and p53- repressed DNA damage response genes in embryonic stem cells. Mol Cell 46:30–42 https://doi.org/10.1016/j.molcel.2012.01.020
53	Z Li, H Lu, W Yang, J Yong, Z-N Zhang, K Zhang, H Deng, Y Xu (2014) Mouse SCNT ESCs have lower somatic mutation load than syngeneic iPSCs. Stem Cell Rep 2:399–405 https://doi.org/10.1016/j.stemcr.2014.02.005
54	L Li, Y Mao, L Zhao, L Li, J, Wu M Zhao, W Du, L Yu, P Jiang (2019) p53 regulation of ammonia metabolism through urea cycle controls polyamine biosynthesis. Nature 567:253–256 https://doi.org/10.1038/s41586-019-0996-7
55	T Lin, C Chao, SI Saito, SJ Mazur, ME Murphy, E Appella, Y Xu (2005) p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression. Nat Cell Biol 7:165–171 https://doi.org/10.1038/ncb1211
56	N Lin, K-Y Chang, Z Li, K Gates, A Rana Zacharia, J Dang, D Zhang, T Han, C-S Yang, J Cunningham Thomaset al. (2014) An evolutionarily conserved long noncoding RNA TUNA controls pluripotency and neural lineage commitment. Mol Cell 53:1005–1019 https://doi.org/10.1016/j.molcel.2014.01.021
57	D Liu, Y Xu (2010) p53, oxidative stress, and aging. Antioxid Redox Signal 15:1669–1678 https://doi.org/10.1089/ars.2010.3644
58	M Mandai, A Watanabe, Y, Kurimoto Y Hirami, C Morinaga, T Daimon, M Fujihara, H Akimaru, N Sakai, Y Shibataet al. (2017) Autologous induced stem-cell-derived retinal cells for macular degeneration. N Engl J Med 376:1038–1046 https://doi.org/10.1056/NEJMoa1608368
59	RM Marión, K Strati, H Li, M Murga, R Blanco, S Ortega, O Fernandez-Capetillo, M Serrano, MA Blasco (2009) A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity. Nature 460:1149–1153 https://doi.org/10.1038/nature08287
60	E Matsa, JH Ahrens, JC Wu (2016) Human induced pluripotent stem cells as a platform for personalized and precision cardiovascular medicine. Physiol Rev 96:1093–1126 https://doi.org/10.1152/physrev.00036.2015
61	D Menendez, A Inga, MA Resnick (2009) The expanding universe of p53 targets. Nat Rev Cancer 9:724–737 https://doi.org/10.1038/nrc2730
62	FT Merkle, S Ghosh, N Kamitaki, J Mitchell, Y Avior, C Mello, S Kashin, S Mekhoubad, D Ilic, M Charltonet al. (2017) Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations. Nature 545:229–233 https://doi.org/10.1038/nature22312
63	PAJ Muller, KH Vousden (2013) p53 mutations in cancer. Nature Cell Biology 15:2–8 https://doi.org/10.1038/ncb2641
64	C Mummery (2011) Induced pluripotent stem cells—a cautionary note. N Engl J Med 364:2160–2162 https://doi.org/10.1056/NEJMcibr1103052
65	M Murphy, J Ahn, KK Walker, WH Hoffman, RM Evans, AJ Levine, DL George (1999) Transcriptional repression by wild-type p53 utilizes histone deacetylases, mediated by interaction with mSin3a. Genes Dev 13:2490–2501 https://doi.org/10.1101/gad.13.19.2490
66	JD Oliner, AY Saiki, S Caenepeel (2016) The role of MDM2 amplification and overexpression in tumorigenesis. Cold Spring Harb Perspect Med 6:a026336 https://doi.org/10.1101/cshperspect.a026336
67	IH Park, R Zhao, JA West, A Yabuuchi, H Huo, TA Ince, PH Lerou, MW Lensch, GQ Daley (2008) Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451:141–146 https://doi.org/10.1038/nature06534
68	R Passier, LW van Laake, CL Mummery (2008) Stem-cell-based therapy and lessons from the heart. Nature 453:322–329 https://doi.org/10.1038/nature07040
69	JL Rinn (2014) lncRNAs: linking RNA to chromatin. Cold Spring Harb Perspect Biol 6:a018614–a018614 https://doi.org/10.1101/cshperspect.a018614
70	NJ Robertson, FA Brook, RL Gardner, SP Cobbold, H Waldmann, PJ Fairchild (2007) Embryonic stem cell-derived tissues are immunogenic but their inherent immune privilege promotes the induction of tolerance. Proc Natl Acad Sci USA 104:20920–20925 https://doi.org/10.1073/pnas.0710265105
71	Z Rong, M Wang, Z Hu, M Stradner, S Zhu, H Kong, H Yi, A Goldrath, Y-G Yang, Y Xuet al. (2014) An effective approach to prevent immune rejection of human ESC-derived allografts. Cell Stem Cell 14:121–130 https://doi.org/10.1016/j.stem.2013.11.014
72	K Sabapathy, DP Lane (2017) Therapeutic targeting of p53: all mutants are equal, but some mutants are more equal than others. Nat Rev Clin Oncol 15:13 https://doi.org/10.1038/nrclinonc.2017.151
73	S Saito, AA Goodarzi, Y Hagashimoto, Y, Noda SP Lees-Miller, E Appella, CW Anderson (2002) ATM mediates phosphorylation at multiple p53 sites, including Ser46, in response to ionizing radiation. J Biol Chem 277(15):12491–12494 https://doi.org/10.1074/jbc.C200093200
74	Y Shi, C Desponts, JT Do, HS Hahm, HR Schˆler, S Ding(2008) Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell 3:568–574 https://doi.org/10.1016/j.stem.2008.10.004
75	SY Shieh, Y Taya, C Prives (1999) DNA damage-inducible phosphorylation of p53 at N-terminal sites including a novel site, Ser20, requires tetramerization. Embo J 18:1815–1823 https://doi.org/10.1093/emboj/18.7.1815
76	ZD Smith, I, Nachman A Regev, A Meissner (2010) Dynamic singlecell imaging of direct reprogramming reveals an early specifying event. Nat Biotechnol 28:521–526 https://doi.org/10.1038/nbt.1632
77	F Soldner, R Jaenisch (2012) iPSC disease modeling. Science 338:1155–1156 https://doi.org/10.1126/science.1227682
78	MJ Son, MY Son, B Seol, MJ Kim, CH Yoo, MK Han, YS Cho (2013) Nicotinamide overcomes pluripotency deficits and reprogramming barriers. Stem Cells 31:1121–1135 https://doi.org/10.1002/stem.1368
79	J Song, C Chao, Y Xu (2007) Ser18 and Ser23 phosphorylation plays synergistic roles in activating p53-dependent neuronal apoptosis. Cell Cycle 6:1411–1413 https://doi.org/10.4161/cc.6.12.4391
80	H Song, S-K Chung, Y Xu (2010) Modeling disease in human ESCs using an efficient BAC-based homologous recombination system. Cell Stem Cell 6:80–89 https://doi.org/10.1016/j.stem.2009.11.016
81	T Soussi, C Béroud (2001) Assessing TP53 status in human tumours to evaluate clinical outcome. Nat Rev Cancer 1:233–239 https://doi.org/10.1038/35106009
82	M Tachibana, P Amato, M Sparman, M Gutierrez Nuria, R Tippner-Hedges, H Ma, E, Kang A Fulati, H-S Lee, H Sritanaudomchaiet al. (2013) Human embryonic stem cells derived by somatic cell nuclear transfer. Cell 153:1228–1238 https://doi.org/10.1016/j.cell.2013.05.006
83	K Takahashi, S Yamanaka (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676 https://doi.org/10.1016/j.cell.2006.07.024
84	Y Tang, J Luo, W Zhang, W Gu (2006) Tip60-dependent acetylation of p53 modulates the decision between cell-cycle arrest and apoptosis. Mol Cell 24:827–839 https://doi.org/10.1016/j.molcel.2006.11.021
85	JA Thomson, J Itskovitz-Eldor, SS Shapiro, MA Waknitz, JJ Swiergiel, VS Marshall, JM Jones (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147 https://doi.org/10.1126/science.282.5391.1145
86	D Todorova, J Kim, S Hamzeinejad, J, He Y Xu (2016) Brief report: immune microenvironment determines the immunogenicity of induced pluripotent stem cell derivatives. Stem Cells 34:510–515 https://doi.org/10.1002/stem.2227
87	G Trigiante, X Lu (2006) ASPP [corrected] and cancer. Nat Rev Cancer 6:217–226 https://doi.org/10.1038/nrc1818
88	A Trounson (2009) Rats, cats, and elephants, but still no unicorn: induced pluripotent stem cells from new species. Cell Stem Cell 4:3–4 https://doi.org/10.1016/j.stem.2008.12.002
89	T Unger, T Juven-Gershon, E Moallem, M Berger, R Vogt Sionov, G Lozano, M Oren, Y Haupt (1999) Critical role for Ser20 of human p53 in the negative regulation of p53 by Mdm2. Embo J 18:1805–1814 https://doi.org/10.1093/emboj/18.7.1805
90	J, Utikal JM Polo, M Stadtfeld, N Maherali, W Kulalert, RM Walsh, A Khalil, JG Rheinwald, K Hochedlinger (2009) Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature 460:1145–1148 https://doi.org/10.1038/nature08285
91	KH Vousden, C Prives (2009) Blinded by the light: the growing complexity of p53. Cell 137:413–431 https://doi.org/10.1016/j.cell.2009.04.037
92	L Weisz, M Oren, V Rotter (2007) Transcription regulation by mutant p53. Oncogene 26:2202–2211 https://doi.org/10.1038/sj.onc.1210294
93	Z Wu, J Earle, S Saito, CW Anderson, E Appella, Y Xu (2002) Mutation of mouse p53 Ser23 and the response to DNA damage. Mol Cell Biol 22:2441–2449 https://doi.org/10.1128/MCB.22.8.2441-2449.2002
94	Y Xu (2005) A new role of p53 in maintaining genetic stability in embryonic stem cells. Cell Cycle 4:363–364 https://doi.org/10.4161/cc.4.3.1529
95	H Xu, B Wang, M Ono, A Kagita, K, Fujii N Sasakawa, T Ueda, P Gee, M Nishikawa, M Nomuraet al. (2019) Targeted disruption of HLA genes via CRISPR-Cas9 generates iPSCs with enhanced immune compatibility. Cell Stem Cell 24:566–578.e567 https://doi.org/10.1016/j.stem.2019.02.005
96	J Yu, MA Vodyanik, K Smuga-Otto, J Antosiewicz-Bourget, JL Frane, S Tian, J Nie, GA Jonsdottir, V Ruotti, R Stewartet al. (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920 https://doi.org/10.1126/science.1151526
97	Z-N Zhang, S-K Chung, Z Xu, Y Xu (2014) Oct4 maintains the pluripotency of human embryonic stem cells by inactivating p53 through Sirt1-mediated deacetylation. Stem Cells 32:157–165 https://doi.org/10.1002/stem.1532
98	T Zhao, Y Xu (2010) P53 and stem cells: new developments and new concerns. Trends Cell Biol 20:170–175 https://doi.org/10.1016/j.tcb.2009.12.004
99	Y Zhao, X Yin, H Qin, F Zhu, H Liu, W Yang, Q Zhang, C Xiang, P Hou, Z Songet al. (2008) Two supporting factors greatly improve the efficiency of human iPSC generation. Cell Stem Cell 3:475–479 https://doi.org/10.1016/j.stem.2008.10.002
100	XY Zhao, W Li, Z Lv, L Liu, M Tong, T Hai, J Hao, CL Guo, QW Ma, L Wanget al. (2009) iPS cells produce viable mice through tetraploid complementation. Nature 461:86–90 https://doi.org/10.1038/nature08267
101	T Zhao, Z-N Zhang, Z Rong, Y Xu (2011) Immunogenicity of induced pluripotent stem cells. Nature 474:212–215 https://doi.org/10.1038/nature10135
102	T Zhao, Z-N Zhang, PD Westenskow, D Todorova, Z Hu, T Lin, Z Rong, J Kim, J He, M Wanget al. (2015) Humanized mice reveal differential immunogenicity of cells derived from autologous induced pluripotent stem cells. Cell Stem Cell 17:353–359 https://doi.org/10.1016/j.stem.2015.07.021

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