The p53 Family and Stem Cell Biology
Stem cells are characterized by the ability to renew themselves (self-renewal) and the capability to generate all the cells within the human body. These features are achieved by a fine-tuned control of proliferation and maintenance of the undifferentiated condition. Transcription factors such as Nanog, Sox, and Oct-4 and extrinsic factors (LIF, BMP, and FGF) have been demonstrated to play a critical role in the regulation of stemness. Because stem cells are under consideration in clinics for cell-based therapy, it is important to understand the molecular mechanisms underlying stemness. In this chapter, we revisit stem cell biology and add a new layer of complexity. In particular, we will discuss the role of the p53 family (p53, p63, and p73) in the regulation of self-renewal, proliferation, and differentiation of stem cells.
KeywordsStem Cell Leukemia Inhibitor Factor Adult Stem Cell Stem Cell Biology Stem Cell Compartment
This work was supported by the Medical Research Council, and by grants from AIRC, Telethon, and Min Sanita’ to G.M.
- Batlle E, Henderson JT, Beghtel H, van den Born MM, Sancho E, Huls G, Meeldijk J, Robertson J, van de Wetering M, Pawson T, Clevers H (2002) Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. Cell 111(2):251–263PubMedCrossRefGoogle Scholar
- Campeau PM, Ah Mew N, Cartier L, Mackay KL, Shaffer LG, Der Kaloustian VM, Thomas MA (2008) Prenatal diagnosis of monosomy 1p36: a focus on brain abnormalities and a review of the literature. Am J Med Genet A 146:3062–3069Google Scholar
- Candi E, Rufini A, Terrinoni A, Dinsdale D, Ranalli M, Paradisi A, De Laurenzi V, Spagnoli LG, Catani MV, Ramadan S, Knight RA, Melino G (2006) Differential roles of p63 isoforms in epidermal development: selective genetic complementation in p63 null mice. Cell Death Differ 13:1037–1047PubMedCrossRefGoogle Scholar
- Dahéron L, Opitz SL, Zaehres H, Lensch MW, Andrews PW, Itskovitz-Eldor J, Daley GQ (2004) LIF/STAT3 signaling fails to maintain self-renewal of human embryonic stem cells. Stem Cells 22(5):770–778, Erratum in: Stem Cells. 2007 Dec;25(12):3273. Lensch, William M [corrected to Lensch, M William]PubMedCrossRefGoogle Scholar
- González-Cano L, Herreros-Villanueva M, Fernández-Alonso R, Ayuso-Sacido Á, Meyer G, García-Verdugo JM, Silva A, Marqués MM, Marín MC (2010) p73 deficiency results in impaired self renewal and premature neuronal differentiation of mouse neural progenitors independently of p53. Cell Death Dis 1:e109. doi: 10.1038/cddis.2010.87 PubMedCrossRefGoogle Scholar
- Kaghad M, Bonnet H, Yang A, Creancier L, Biscan JC, Valent A, Minty A, Chalon P, Lelias JM, Dumont X, Ferrara P, McKeon F, Caput D (1997) Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell 90:809–819PubMedCrossRefGoogle Scholar
- Loh YH, Wu Q, Chew JL, Vega VB, Zhang W, Chen X, Bourque G, George J, Leong B, Liu J, Wong KY, Sung KW, Lee CW, Zhao XD, Chiu KP, Lipovich L, Kuznetsov VA, Robson P, Stanton LW, Wei CL, Ruan Y, Lim B, Ng HH (2006) The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet 38:431–440PubMedCrossRefGoogle Scholar
- Machold R, Hayashi S, Rutlin M, Muzumdar MD, Nery S, Corbin JG, Gritli-Linde A, Dellovade T, Porter JA, Rubin LL, Dudek H, McMahon AP, Fishell G (2003) Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches. Neuron 39(6):937–950, Erratum in: Neuron. 2003 Sep 25;40(1):189PubMedCrossRefGoogle Scholar
- Zhao Y, Yin X, Qin H, Zhu F, Liu H, Yang W, Zhang Q, Xiang C, Hou P, Song Z, Liu Y, Yong J, Zhang P, Cai J, Liu M, Li H, Li Y, Qu X, Cui K, Zhang W, Xiang T, Wu Y, Zhao Y, Liu C, Yu C, Yuan K, Lou J, Ding M, Deng H (2008) Two supporting factors greatly improve the efficiency of human iPSC generation. Cell Stem Cell 3:475–479PubMedCrossRefGoogle Scholar