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Regulatory Networks in Stem Cells pp 67–74Cite as

Genomic Stability in Stem Cells

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Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

Abstract

Accumulated data suggest that the unique function of stem cells to self-renew is under the strong control of a sensor system detecting potential threats to genomic integrity. Reactive oxygen species, the most significant mutagens in stem cells, when elevated, activate the protective mechanisms blocking self-renewal and at the same time serve as a signal stimulating stem cell differentiation. Based on studies performed primarily on hematopoietic stem cells and embryonic stem cells, we outline the signaling networks connecting the ATM, MAPK14 (p38) and FRAP1 (mTOR) protein kinases, the p53 tumor suppressor, the PTEN phosphatase, and the TEL, NF\(\upkappa\)B, FoxO, and HIF transcription factor families as a potential stress-controlled differentiation mechanism regulating stem cell fate decisions. An intriguing observation to come from these studies is that stem cell self-renewal capacity appears to be pharmacologically preserved by anti-oxidative agents.

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References

  1. Bradford GB, Williams B, Rossi R, Bertoncello I. Quiescence, cycling, and turnover in the primitive hematopoietic stem cell compartment. Exp Hematol. 1997;25:445–53.

    PubMed  CAS  Google Scholar 

  2. Cheshier SH, Morrison SJ, Liao X, Weissman IL. In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells. Proc Natl Acad Sci U S A. 1999;96:3120–5.

    Article  PubMed  CAS  Google Scholar 

  3. Vickers M, Brown GC, Cologne JB, Kyoizumi S. Modelling haemopoietic stem cell division by analysis of mutant red cells. Br J Haematol. 2000;110:54–62.

    Article  PubMed  CAS  Google Scholar 

  4. Vilenchik MM, Knudson AG. Endogenous DNA double-strand breaks: production, fidelity of repair, and induction of cancer. Proc Natl Acad Sci U S A. 2003;100:12871–6.

    Article  PubMed  CAS  Google Scholar 

  5. Cervantes RB, Stringer JR, Shao C, Tischfield JA, Stambrook PJ. Embryonic stem cells and somatic cells differ in mutation frequency and type. Proc Natl Acad Sci U S A. 2002;99: 3586–90.

    Article  PubMed  CAS  Google Scholar 

  6. Hong Y, Cervantes RB, Tichy E, Tischfield JA, Stambrook PJ. Protecting genomic integrity in somatic cells and embryonic stem cells. Mutat Res. 2007;614:48–55.

    PubMed  CAS  Google Scholar 

  7. Cairns J. Cancer and the immortal strand hypothesis. Genetics. 2006;174:1069–72.

    Article  PubMed  CAS  Google Scholar 

  8. Potten CS, Owen G, Booth D. Intestinal stem cells protect their genome by selective segregation of template DNA strands. J Cell Sci. 2002;115:2381–8.

    PubMed  CAS  Google Scholar 

  9. Karpowicz P, Morshead C, Kam A, et al. Support for the immortal strand hypothesis: neural stem cells partition DNA asymmetrically in vitro. J Cell Biol. 2005;170:721–32.

    Article  PubMed  CAS  Google Scholar 

  10. Shinin V, Gayraud-Morel B, Gomes D, Tajbakhsh S. Asymmetric division and cosegregation of template DNA strands in adult muscle satellite cells. Nat Cell Biol. 2006;8:677–87.

    Article  PubMed  CAS  Google Scholar 

  11. Conboy MJ, Karasov AO, Rando TA. High incidence of non-random template strand segregation and asymmetric fate determination in dividing stem cells and their progeny. PLoS Biol. 2007;5:e102.

    Article  PubMed  Google Scholar 

  12. Kiel MJ, He S, Ashkenazi R, et al. Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU. Nature. 2007;449:238–42.

    Article  PubMed  CAS  Google Scholar 

  13. Bunting KD, Hawley RG. Integrative molecular and developmental biology of adult stem cells. Biol Cell. 2003;95:563–78.

    Article  PubMed  CAS  Google Scholar 

  14. Saretzki G, Armstrong L, Leake A, Lako M, von ZT. Stress defense in murine embryonic stem cells is superior to that of various differentiated murine cells. Stem Cells. 2004;22:962–71.

    Article  PubMed  CAS  Google Scholar 

  15. Eaker SS, Hawley TS, Ramezani A, Hawley RG. Detection and enrichment of hematopoietic stem cells by side population phenotype. Methods Mol Biol. 2004;263:161–80.

    PubMed  Google Scholar 

  16. Hawley RG, Ramezani A, Hawley TS. Hematopoietic stem cells. Methods Enzymol. 2006;419:149–79.

    Article  PubMed  CAS  Google Scholar 

  17. Unwin RD, Smith DL, Blinco D, et al. Quantitative proteomics reveals posttranslational control as a regulatory factor in primary hematopoietic stem cells. Blood. 2006;107:4687–94.

    Article  PubMed  CAS  Google Scholar 

  18. Saretzki G, Walter T, Atkinson S, et al. Downregulation of multiple stress defense mechanisms during differentiation of human embryonic stem cells. Stem Cells. 2008;26:455–64.

    Article  PubMed  CAS  Google Scholar 

  19. Suda T, Arai F, Hirao A. Hematopoietic stem cells and their niche. Trends Immunol. 2005;26:426–33.

    Article  PubMed  CAS  Google Scholar 

  20. Zhang W, Remenyik E, Zelterman D, Brash DE, Wikonkal NM. Escaping the stem cell compartment: sustained UVB exposure allows p53-mutant keratinocytes to colonize adjacent epidermal proliferating units without incurring additional mutations. Proc Natl Acad Sci U S A. 2001;98:13948–53.

    Article  PubMed  CAS  Google Scholar 

  21. Khanna KK, Jackson SP. DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet. 2001;27:247–54.

    Article  PubMed  CAS  Google Scholar 

  22. Aladjem MI, Spike BT, Rodewald LW, et al. ES cells do not activate p53-dependent stress responses and undergo p53-independent apoptosis in response to DNA damage. Curr Biol. 1998;8:145–55.

    Article  PubMed  CAS  Google Scholar 

  23. Donahue SL, Lin Q, Cao S, Ruley HE. Carcinogens induce genome-wide loss of heterozygosity in normal stem cells without persistent chromosomal instability. Proc Natl Acad Sci U S A. 2006;103:11642–6.

    Article  PubMed  CAS  Google Scholar 

  24. Nijnik A, Woodbine L, Marchetti C, et al. DNA repair is limiting for haematopoietic stem cells during ageing. Nature. 2007;447:686–90.

    Article  PubMed  CAS  Google Scholar 

  25. Rossi DJ, Bryder D, Seita J, Nussenzweig A, Hoeijmakers J, Weissman IL. Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature. 2007;447:725–9.

    Article  PubMed  CAS  Google Scholar 

  26. Chow DC, Wenning LA, Miller WM, Papoutsakis ET. Modeling pO(2) distributions in the bone marrow hematopoietic compartment. I. Krogh’s model. Biophys J. 2001;81:675–84.

    Article  PubMed  CAS  Google Scholar 

  27. Chow DC, Wenning LA, Miller WM, Papoutsakis ET. Modeling pO(2) distributions in the bone marrow hematopoietic compartment. II. Modified Kroghian models. Biophys J. 2001;81: 685–96.

    Article  PubMed  CAS  Google Scholar 

  28. Parmar K, Mauch P, Vergilio JA, Sackstein R, Down JD. Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia. Proc Natl Acad Sci U S A. 2007;104: 5431–6.

    Article  PubMed  CAS  Google Scholar 

  29. Piccoli C, Ria R, Scrima R, et al. Characterization of mitochondrial and extra-mitochondrial oxygen consuming reactions in human hematopoietic stem cells. Novel evidence of the occurrence of NAD(P)H oxidase activity. J Biol Chem. 2005;280: 26467–76.

    Article  PubMed  CAS  Google Scholar 

  30. Piccoli C, D’Aprile A, Ripoli M, et al. Bone-marrow derived hematopoietic stem/progenitor cells express multiple isoforms of NADPH oxidase and produce constitutively reactive oxygen species. Biochem Biophys Res Commun. 2007;353:965–72.

    Article  PubMed  CAS  Google Scholar 

  31. Cho YM, Kwon S, Pak YK, et al. Dynamic changes in mitochondrial biogenesis and antioxidant enzymes during the spontaneous differentiation of human embryonic stem cells. Biochem Biophys Res Commun. 2006;348:1472–8.

    Article  PubMed  CAS  Google Scholar 

  32. Schmelter M, Ateghang B, Helmig S, Wartenberg M, Sauer H. Embryonic stem cells utilize reactive oxygen species as transducers of mechanical strain-induced cardiovascular differentiation. FASEB J. 2006;20:1182–4.

    Article  PubMed  CAS  Google Scholar 

  33. Madhavan L, Ourednik V, Ourednik J. Increased “vigilance” of antioxidant mechanisms in neural stem cells potentiates their capability to resist oxidative stress. Stem Cells. 2006;24:2110–9.

    Article  PubMed  CAS  Google Scholar 

  34. Wang N, Xie K, Huo S, Zhao J, Zhang S, Miao J. Suppressing phosphatidylcholine-specific phospholipase C and elevating ROS level, NADPH oxidase activity and Rb level induced neuronal differentiation in mesenchymal stem cells. J Cell Biochem. 2007;100:1548–57.

    Article  PubMed  CAS  Google Scholar 

  35. Finkel T. Redox-dependent signal transduction. FEBS Lett. 2000;476:52–4.

    Article  PubMed  CAS  Google Scholar 

  36. Poulsen HE, Jensen BR, Weimann A, Jensen SA, Sorensen M, Loft S. Antioxidants, DNA damage and gene expression. Free Radic Res. 2000;33 Suppl:S33–9.

    PubMed  CAS  Google Scholar 

  37. Sattler M, Winkler T, Verma S, et al. Hematopoietic growth factors signal through the formation of reactive oxygen species. Blood. 1999;93:2928–35.

    PubMed  CAS  Google Scholar 

  38. Ito K, Hirao A, Arai F, et al. Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature. 2004;431:997–1002.

    Article  PubMed  CAS  Google Scholar 

  39. Barzilai A, Rotman G, Shiloh Y. ATM deficiency and oxidative stress: a new dimension of defective response to DNA damage. DNA Repair (Amst). 2002;1:3–25.

    Article  CAS  Google Scholar 

  40. Ito K, Hirao A, Arai F, et al. Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med. 2006;12:446–51.

    Article  PubMed  CAS  Google Scholar 

  41. Emerling BM, Platanias LC, Black E, Nebreda AR, Davis RJ, Chandel NS. Mitochondrial reactive oxygen species activation of p38 mitogen-activated protein kinase is required for hypoxia signaling. Mol Cell Biol. 2005;25:4853–62.

    Article  PubMed  CAS  Google Scholar 

  42. Sanchez-Prieto R, Rojas JM, Taya Y, Gutkind JS. A role for the p38 mitogen-acitvated protein kinase pathway in the transcriptional activation of p53 on genotoxic stress by chemotherapeutic agents. Cancer Res. 2000;60:2464–72.

    PubMed  CAS  Google Scholar 

  43. Ryan S, McNicholas WT, Taylor CT. A critical role for p38 map kinase in NF-kappaB signaling during intermittent hypoxia/reoxygenation. Biochem Biophys Res Commun. 2007;355:728–33.

    Article  PubMed  CAS  Google Scholar 

  44. Hock H, Meade E, Medeiros S, et al. Tel/Etv6 is an essential and selective regulator of adult hematopoietic stem cell survival. Genes Dev. 2004;18:2336–41.

    Article  PubMed  CAS  Google Scholar 

  45. Arai H, Maki K, Waga K, et al. Functional regulation of TEL by p38-induced phosphorylation. Biochem Biophys Res Commun. 2002;299:116–25.

    Article  PubMed  CAS  Google Scholar 

  46. Seita J, Ema H, Ooehara J, et al. Lnk negatively regulates self-renewal of hematopoietic stem cells by modifying thrombopoietin-mediated signal transduction. Proc Natl Acad Sci U S A. 2007;104:2349–54.

    Article  PubMed  CAS  Google Scholar 

  47. Bae IH, Kang SW, Yoon SH, Um HD. Cellular components involved in the cell death induced by cisplatin in the absence of p53 activation. Oncol Rep. 2006;15:1175–80.

    PubMed  CAS  Google Scholar 

  48. Caspari T. How to activate p53. Curr Biol. 2000;10:R315–7.

    Article  PubMed  CAS  Google Scholar 

  49. Chen C, Shimizu S, Tsujimoto Y, Motoyama N. Chk2 regulates transcription-independent p53-mediated apoptosis in response to DNA damage. Biochem Biophys Res Commun. 2005;333: 427–31.

    Article  PubMed  CAS  Google Scholar 

  50. Khanna KK, Keating KE, Kozlov S, et al. ATM associates with and phosphorylates p53: mapping the region of interaction. Nat Genet. 1998;20:398–400.

    Article  PubMed  CAS  Google Scholar 

  51. Khosravi R, Maya R, Gottlieb T, Oren M, Shiloh Y, Shkedy D. Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage. Proc Natl Acad Sci U S A. 1999;96:14973–7.

    Article  PubMed  CAS  Google Scholar 

  52. Budanov AV, Sablina AA, Feinstein E, Koonin EV, Chumakov PM. Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD. Science. 2004;304:596–600.

    Article  PubMed  CAS  Google Scholar 

  53. Sablina AA, Budanov AV, Ilyinskaya GV, Agapova LS, Kravchenko JE, Chumakov PM. The antioxidant function of the p53 tumor suppressor. Nat Med. 2005;11:1306–13.

    Article  PubMed  CAS  Google Scholar 

  54. Merok JR, Lansita JA, Tunstead JR, Sherley JL. Cosegregation of chromosomes containing immortal DNA strands in cells that cycle with asymmetric stem cell kinetics. Cancer Res. 2002;62:6791–5.

    PubMed  CAS  Google Scholar 

  55. Rambhatla L, Ram-Mohan S, Cheng JJ, Sherley JL. Immortal DNA strand cosegregation requires p53/IMPDH-dependent asymmetric self-renewal associated with adult stem cells. Cancer Res. 2005;65:3155–61.

    PubMed  CAS  Google Scholar 

  56. Meletis K, Wirta V, Hede SM, Nister M, Lundeberg J, Frisen J. p53 suppresses the self-renewal of adult neural stem cells. Development. 2006;133:363–9.

    Article  PubMed  CAS  Google Scholar 

  57. Dumble M, Moore L, Chambers SM, et al. The impact of altered p53 dosage on hematopoietic stem cell dynamics during aging. Blood. 2007;109:1736–42.

    Article  PubMed  CAS  Google Scholar 

  58. Cheng T, Rodrigues N, Shen H, et al. Hematopoietic stem cell quiescence maintained by p21cip1/waf1. Science. 2000;287:1804–8.

    Article  PubMed  CAS  Google Scholar 

  59. Tyner SD, Venkatachalam S, Choi J, et al. p53 mutant mice that display early ageing-associated phenotypes. Nature. 2002;415:45–53.

    Article  PubMed  CAS  Google Scholar 

  60. Maier B, Gluba W, Bernier B, et al. Modulation of mammalian life span by the short isoform of p53. Genes Dev. 2004;18:306–19.

    Article  PubMed  CAS  Google Scholar 

  61. Yilmaz OH, Valdez R, Theisen BK, et al. Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature. 2006;441:475–82.

    Article  PubMed  CAS  Google Scholar 

  62. Cho SH, Lee CH, Ahn Y, et al. Redox regulation of PTEN and protein tyrosine phosphatases in H(2)O(2) mediated cell signaling. FEBS Lett. 2004;560:7–13.

    Article  PubMed  CAS  Google Scholar 

  63. Salmeen A, Barford D. Functions and mechanisms of redox regulation of cysteine-based phosphatases. Antioxid Redox Signal. 2005;7:560–77.

    Article  PubMed  CAS  Google Scholar 

  64. Barthel A, Klotz LO. Phosphoinositide 3-kinase signaling in the cellular response to oxidative stress. Biol Chem. 2005;386: 207–16.

    Article  PubMed  CAS  Google Scholar 

  65. Abraham RT, Gibbons JJ. The mammalian target of rapamycin signaling pathway: twists and turns in the road to cancer therapy. Clin Cancer Res. 2007;13:3109–14.

    Article  PubMed  CAS  Google Scholar 

  66. Brugarolas J, Lei K, Hurley RL, et al. Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev. 2004;18:2893–904.

    Article  PubMed  CAS  Google Scholar 

  67. Tothova Z, Kollipara R, Huntly BJ, et al. FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell. 2007;128:325–39.

    Article  PubMed  CAS  Google Scholar 

  68. Jang YY, Sharkis SJ. A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche. Blood. 2007;110:3056–63

    Article  PubMed  CAS  Google Scholar 

  69. Fritz G, Grosch S, Tomicic M, Kaina B. APE/Ref-1 and the mammalian response to genotoxic stress. Toxicology. 2003;193: 67–78.

    Article  PubMed  CAS  Google Scholar 

  70. Zou GM, Luo MH, Reed A, Kelley MR, Yoder MC. Ape1 regulates hematopoietic differentiation of embryonic stem cells through its redox functional domain. Blood. 2007;109:1917–22.

    Article  PubMed  CAS  Google Scholar 

  71. Pyatt DW, Stillman WS, Yang Y, Gross S, Zheng JH, Irons RD. An essential role for NF-kappaB in human CD34(+) bone marrow cell survival. Blood. 1999;93:3302–8.

    PubMed  CAS  Google Scholar 

  72. Opferman JT, Iwasaki H, Ong CC, et al. Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem cells. Science. 2005;307:1101–4.

    Article  PubMed  CAS  Google Scholar 

  73. Domen J, Weissman IL. Hematopoietic stem cells need two signals to prevent apoptosis; BCL-2 can provide one of these, Kitl/c-Kit signaling the other. J Exp Med. 2000;192:1707–18.

    Article  PubMed  CAS  Google Scholar 

  74. Domen J, Cheshier SH, Weissman IL. The role of apoptosis in the regulation of hematopoietic stem cells: overexpression of Bcl-2 increases both their number and repopulation potential. J Exp Med. 2000;191:253–64.

    Article  PubMed  CAS  Google Scholar 

  75. Nakata S, Matsumura I, Tanaka H, et al. NF-kappaB family proteins participate in multiple steps of hematopoiesis through elimination of reactive oxygen species. J Biol Chem. 2004;279: 55578–86.

    Article  PubMed  CAS  Google Scholar 

  76. Tanaka H, Matsumura I, Ezoe S, et al. E2F1 and c-Myc potentiate apoptosis through inhibition of NF-kappaB activity that facilitates MnSOD-mediated ROS elimination. Mol Cell. 2002;9:1017–29.

    Article  PubMed  CAS  Google Scholar 

  77. Korn SH, Wouters EF, Vos N, Janssen-Heininger YM. Cytokine-induced activation of nuclear factor-kappa B is inhibited by hydrogen peroxide through oxidative inactivation of IkappaB kinase. J Biol Chem. 2001;276:35693–700.

    Article  PubMed  CAS  Google Scholar 

  78. Kamata H, Manabe T, Oka S, Kamata K, Hirata H. Hydrogen peroxide activates IkappaB kinases through phosphorylation of serine residues in the activation loops. FEBS Lett. 2002;519: 231–7.

    Article  PubMed  CAS  Google Scholar 

  79. Bardos JI, Ashcroft M. Negative and positive regulation of HIF-1: a complex network. Biochim Biophys Acta. 2005;1755:107–20.

    PubMed  CAS  Google Scholar 

  80. Bakker WJ, Harris IS, Mak TW. FOXO3a is activated in response to hypoxic stress and inhibits HIF1-induced apoptosis via regulation of CITED2. Mol Cell. 2007;28:941–53.

    Article  PubMed  CAS  Google Scholar 

  81. Nishi H, Nakada T, Kyo S, Inoue M, Shay JW, Isaka K. Hypoxia-inducible factor 1 mediates upregulation of telomerase (hTERT). Mol Cell Biol. 2004;24:6076–83.

    Article  PubMed  CAS  Google Scholar 

  82. Yatabe N, Kyo S, Maida Y, et al. HIF-1-mediated activation of telomerase in cervical cancer cells. Oncogene. 2004;23:3708–15.

    Article  PubMed  CAS  Google Scholar 

  83. Bonello S, Zahringer C, BelAiba RS, et al. Reactive oxygen species activate the HIF-1alpha promoter via a functional NFkappaB site. Arterioscler Thromb Vasc Biol. 2007;27:755–61.

    Article  PubMed  CAS  Google Scholar 

  84. Hudson CC, Liu M, Chiang GG, et al. Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin. Mol Cell Biol. 2002;22:7004–14.

    Article  PubMed  CAS  Google Scholar 

  85. Wartenberg M, Gronczynska S, Bekhite MM, et al. Regulation of the multidrug resistance transporter P-glycoprotein in multicellular prostate tumor spheroids by hyperthermia and reactive oxygen species. Int J Cancer. 2005;113:229–40.

    Article  PubMed  CAS  Google Scholar 

  86. Goyal P, Weissmann N, Grimminger F, et al. Upregulation of NAD(P)H oxidase 1 in hypoxia activates hypoxia-inducible factor 1 via increase in reactive oxygen species. Free Radic Biol Med. 2004;36:1279–88.

    Article  PubMed  CAS  Google Scholar 

  87. Gustafsson MV, Zheng X, Pereira T, et al. Hypoxia requires notch signaling to maintain the undifferentiated cell state. Dev Cell. 2005;9:617–28.

    Article  PubMed  CAS  Google Scholar 

  88. Suzuki T, Chiba S. Notch signaling in hematopoietic stem cells. Int J Hematol. 2005;82:285–94.

    Article  PubMed  CAS  Google Scholar 

  89. Shi Y, Sun G, Zhao C, Stewart R. Neural stem cell self-renewal. Crit Rev Oncol Hematol. 2008;65:43–53.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Anatomy and Regenerative Biology, The George Washington University, 2300 I Street NW, 20037, Washington, DC

    Robert G. Hawley

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  1. Irene Riz
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Correspondence to Robert G. Hawley .

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Editors and Affiliations

  1. Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Vinagolu K. Rajasekhar MSc, MPhil, PhD

  2. Invitrogen Corporation, Frederick, MD, USA

    Mohan C. Vemuri Ph.D.

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© 2009 Humana Press, a part of Springer Science+Business Media, LLC, a part of Springer Science+Business Media, LLC

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Riz, I., Hawley, R.G. (2009). Genomic Stability in Stem Cells. In: Rajasekhar, V.K., Vemuri, M.C. (eds) Regulatory Networks in Stem Cells. Stem Cell Biology and Regenerative Medicine. Humana Press. https://doi.org/10.1007/978-1-60327-227-8_6

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