1932

Abstract

Various stem cells in the body are tasked with maintaining tissue homeostasis throughout the life of an organism and thus must be resilient to intrinsic and extrinsic challenges such as infection and injury. Crucial to these challenges is genome maintenance because a high mutational load and persistent DNA lesions impact the production of essential gene products at proper levels and compromise optimal stem cell renewal and differentiation. Genome maintenance requires a robust and well-regulated DNA damage response suited to maintaining specific niches and tissues. In this review, we explore the similarities and differences between diverse stem cell types derived from (or preceding) all germ layers, including extraembryonic tissues. These cells utilize different strategies, including implementation of robust repair mechanisms, modulation of cell cycle checkpoints best suited to eliminating compromised cells, minimization of cell divisions, and differentiation in response to excessive damage.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-genet-072920-022154
2022-11-30
2024-04-15
Loading full text...

Full text loading...

/deliver/fulltext/genet/56/1/annurev-genet-072920-022154.html?itemId=/content/journals/10.1146/annurev-genet-072920-022154&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Adam RC, Yang H, Ge Y, Lien W-H, Wang P et al. 2018. Temporal layering of signaling effectors drives chromatin remodeling during hair follicle stem cell lineage progression. Cell Stem Cell 22:3398–413.e7
    [Google Scholar]
  2. 2.
    Aguirre N, Beal MF, Matson WR, Bogdanov MB. 2005. Increased oxidative damage to DNA in an animal model of amyotrophic lateral sclerosis. Free Radic. Res. 39:4383–88
    [Google Scholar]
  3. 3.
    Ahlenius H, Visan V, Kokaia M, Lindvall O, Kokaia Z. 2009. Neural stem and progenitor cells retain their potential for proliferation and differentiation into functional neurons despite lower number in aged brain. J. Neurosci. 29:144408–19
    [Google Scholar]
  4. 4.
    Ahuja AK, Jodkowska K, Teloni F, Bizard AH, Zellweger R et al. 2016. A short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells. Nat. Commun. 7:10660
    [Google Scholar]
  5. 5.
    Aladjem MI, Spike BT, Rodewald LW, Hope TJ, Klemm M et al. 1998. ES cells do not activate p53-dependent stress responses and undergo p53-independent apoptosis in response to DNA damage. Curr. Biol. 8:3145–55
    [Google Scholar]
  6. 6.
    Allawzi A, Elajaili H, Redente EF, Nozik-Grayck E. 2019. Oxidative toxicology of bleomycin: role of the extracellular redox environment. Curr. Opin. Toxicol. 13:68–73
    [Google Scholar]
  7. 7.
    Alvarez S, Díaz M, Flach J, Rodriguez-Acebes S, López-Contreras AJ et al. 2015. Replication stress caused by low MCM expression limits fetal erythropoiesis and hematopoietic stem cell functionality. Nat. Commun. 6:8548
    [Google Scholar]
  8. 8.
    Bae T, Tomasini L, Mariani J, Zhou B, Roychowdhury T et al. 2018. Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis. Science 359:6375550–55
    [Google Scholar]
  9. 9.
    Bailey KJ, Maslov AY, Pruitt SC. 2004. Accumulation of mutations and somatic selection in aging neural stem/progenitor cells. Aging Cell 3:6391–97
    [Google Scholar]
  10. 10.
    Barazzuol L, Ju L, Jeggo PA. 2017. A coordinated DNA damage response promotes adult quiescent neural stem cell activation. PLOS Biol 15:5e2001264
    [Google Scholar]
  11. 11.
    Barker N. 2014. Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration. Nat. Rev. Mol. Cell Biol. 15:119–33
    [Google Scholar]
  12. 12.
    Barker N, van Es JH, Kuipers J, Kujala P, van den Born M et al. 2007. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449:71651003–7
    [Google Scholar]
  13. 13.
    Barzilai A. 2007. The contribution of the DNA damage response to neuronal viability. Antioxid. Redox Signal. 9:2211–18
    [Google Scholar]
  14. 14.
    Beerman I, Bhattacharya D, Zandi S, Sigvardsson M, Weissman IL et al. 2010. Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion. PNAS 107:125465–70
    [Google Scholar]
  15. 15.
    Beerman I, Seita J, Inlay MA, Weissman IL, Rossi DJ. 2014. Quiescent hematopoietic stem cells accumulate DNA damage during aging that is repaired upon entry into cell cycle. Cell Stem Cell 15:137–50
    [Google Scholar]
  16. 16.
    Blokzijl F, de Ligt J, Jager M, Sasselli V, Roerink S et al. 2016. Tissue-specific mutation accumulation in human adult stem cells during life. Nature 538:7624260–64
    [Google Scholar]
  17. 17.
    Bloom JC, Schimenti JC. 2020. Sexually dimorphic DNA damage responses and mutation avoidance in the mouse germline. Genes Dev 34:23–241637–49
    [Google Scholar]
  18. 18.
    Bonaguidi MA, Song J, Ming G, Song H 2012. A unifying hypothesis on mammalian neural stem cell properties in the adult hippocampus. Curr. Opin. Neurobiol. 22:5754–61
    [Google Scholar]
  19. 19.
    Cervantes RB, Stringer JR, Shao C, Tischfield JA, Stambrook PJ. 2002. Embryonic stem cells and somatic cells differ in mutation frequency and type. PNAS 99:63586–90
    [Google Scholar]
  20. 20.
    Chen H, Goodus MT, de Toledo SM, Azzam EI, Levison SW, Souayah N. 2015. Ionizing radiation perturbs cell cycle progression of neural precursors in the subventricular zone without affecting their long-term self-renewal. ASN Neuro 7:31759091415578026
    [Google Scholar]
  21. 21.
    Chuang C-H, Wallace MD, Abratte C, Southard T, Schimenti JC. 2010. Incremental genetic perturbations to MCM2-7 expression and subcellular distribution reveal exquisite sensitivity of mice to DNA replication stress. PLOS Genet 6:9e1001110
    [Google Scholar]
  22. 22.
    Cleaver JE, Lam ET, Revet I. 2009. Disorders of nucleotide excision repair: the genetic and molecular basis of heterogeneity. Nat. Rev. Genet. 10:11756–68
    [Google Scholar]
  23. 23.
    Cooper DJ, Chen I-C, Hernandez C, Wang Y, Walter CA, McCarrey JR. 2017. Pluripotent cells display enhanced resistance to mutagenesis. Stem Cell Res 19:113–17
    [Google Scholar]
  24. 24.
    Coorens THH, Oliver TRW, Sanghvi R, Sovio U, Cook E et al. 2021. Inherent mosaicism and extensive mutation of human placentas. Nature 592:785280–85
    [Google Scholar]
  25. 25.
    Dong C, Wang X, Sun L, Zhu L, Yang D et al. 2021. ATM modulates subventricular zone neural stem cell maintenance and senescence through notch signaling pathway. Stem Cell Res 58:102618
    [Google Scholar]
  26. 26.
    Dong X, Zhang L, Milholland B, Lee M, Maslov AY et al. 2017. Accurate identification of single-nucleotide variants in whole-genome-amplified single cells. Nat. Methods 14:5491–93
    [Google Scholar]
  27. 27.
    Felgentreff K, Du L, Weinacht KG, Dobbs K, Bartish M et al. 2014. Differential role of nonhomologous end joining factors in the generation, DNA damage response, and myeloid differentiation of human induced pluripotent stem cells. PNAS 111:248889–94
    [Google Scholar]
  28. 28.
    Fevr T, Robine S, Louvard D, Huelsken J. 2007. Wnt/β-catenin is essential for intestinal homeostasis and maintenance of intestinal stem cells. Mol. Cell. Biol. 27:217551–59
    [Google Scholar]
  29. 29.
    Garaycoechea JI, Crossan GP, Langevin F, Daly M, Arends MJ, Patel KJ. 2012. Genotoxic consequences of endogenous aldehydes on mouse haematopoietic stem cell function. Nature 489:7417571–75
    [Google Scholar]
  30. 30.
    Ginsburg M, Snow MH, McLaren A. 1990. Primordial germ cells in the mouse embryo during gastrulation. Development 110:2521–28
    [Google Scholar]
  31. 31.
    Gnani D, Crippa S, Della Volpe L, Rossella V, Conti A et al. 2019. An early-senescence state in aged mesenchymal stromal cells contributes to hematopoietic stem and progenitor cell clonogenic impairment through the activation of a pro-inflammatory program. Aging Cell 18:3e12933
    [Google Scholar]
  32. 32.
    González F, Georgieva D, Vanoli F, Shi Z-D, Stadtfeld M et al. 2013. Homologous recombination DNA repair genes play a critical role in reprogramming to a pluripotent state. Cell Rep 3:3651–60
    [Google Scholar]
  33. 33.
    Gore A, Li Z, Fung H-L, Young JE, Agarwal S et al. 2011. Somatic coding mutations in human induced pluripotent stem cells. Nature 471:733663–67
    [Google Scholar]
  34. 34.
    Gronke K, Hernández PP, Zimmermann J, Klose CSN, Kofoed-Branzk M et al. 2019. Interleukin-22 protects intestinal stem cells against genotoxic stress. Nature 566:7743249–53
    [Google Scholar]
  35. 35.
    Hannibal RL, Baker JC. 2016. Selective amplification of the genome surrounding key placental genes in trophoblast giant cells. Curr. Biol. 26:2230–36
    [Google Scholar]
  36. 36.
    Hannibal RL, Chuong EB, Rivera-Mulia JC, Gilbert DM, Valouev A, Baker JC. 2014. Copy number variation is a fundamental aspect of the placental genome. PLOS Genet 10:5e1004290
    [Google Scholar]
  37. 37.
    Hill RJ, Crossan GP. 2019. DNA cross-link repair safeguards genomic stability during premeiotic germ cell development. Nat. Genet. 51:81283–94
    [Google Scholar]
  38. 38.
    Hong Y, Stambrook PJ. 2004. Restoration of an absent G1 arrest and protection from apoptosis in embryonic stem cells after ionizing radiation. PNAS 101:4014443–48
    [Google Scholar]
  39. 39.
    Hsu Y-C, Fuchs E. 2022. Building and maintaining the skin. Cold Spring Harb. Perspect. Biol. 14:a040840
    [Google Scholar]
  40. 40.
    Hsu Y-C, Li L, Fuchs E 2014. Transit-amplifying cells orchestrate stem cell activity and tissue regeneration. Cell 157:4935–49
    [Google Scholar]
  41. 41.
    Hu D, Cross JC. 2010. Development and function of trophoblast giant cells in the rodent placenta. Int. J. Dev. Biol. 54:2–3341–54
    [Google Scholar]
  42. 42.
    Hua G, Thin TH, Feldman R, Haimovitz-Friedman A, Clevers H et al. 2012. Crypt base columnar stem cells in small intestines of mice are radioresistant. Gastroenterology 143:51266–76
    [Google Scholar]
  43. 43.
    Hussein SM, Batada NN, Vuoristo S, Ching RW, Autio R et al. 2011. Copy number variation and selection during reprogramming to pluripotency. Nature 471:733658–62
    [Google Scholar]
  44. 44.
    Inoue K, Aoi N, Sato T, Yamauchi Y, Suga H et al. 2009. Differential expression of stem-cell-associated markers in human hair follicle epithelial cells. Lab. Invest. 89:8844–56
    [Google Scholar]
  45. 45.
    Izadpanah R, Trygg C, Patel B, Kriedt C, Dufour J et al. 2006. Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue. J. Cell. Biochem. 99:51285–97
    [Google Scholar]
  46. 46.
    Ji J, Sharma V, Qi S, Guarch ME, Zhao P et al. 2014. Antioxidant supplementation reduces genomic aberrations in human induced pluripotent stem cells. Stem Cell Rep 2:144–51
    [Google Scholar]
  47. 47.
    Jiang J, Miao Y, Xiao S, Zhang Z, Hu Z. 2014. DAPT in the control of human hair follicle stem cell proliferation and differentiation. Postepy Dermatol. Alergol. 31:4201–6
    [Google Scholar]
  48. 48.
    Kalamakis G, Brüne D, Ravichandran S, Bolz J, Fan W et al. 2019. Quiescence modulates stem cell maintenance and regenerative capacity in the aging brain. Cell 176:61407–19.e14
    [Google Scholar]
  49. 49.
    Kaur A, Lim JYS, Sepramaniam S, Patnaik S, Harmston N et al. 2021. WNT inhibition creates a BRCA-like state in Wnt-addicted cancer. EMBO Mol. Med. 13:4e13349
    [Google Scholar]
  50. 50.
    Kim C-K, Yang VW, Bialkowska AB. 2017. The role of intestinal stem cells in epithelial regeneration following radiation-induced gut injury. Curr. Stem Cell Rep. 3:4320–32
    [Google Scholar]
  51. 51.
    Kim JY, Ohn J, Yoon J-S, Kang BM, Park M et al. 2019. Priming mobilization of hair follicle stem cells triggers permanent loss of regeneration after alkylating chemotherapy. Nat. Commun. 10:13694
    [Google Scholar]
  52. 52.
    Kohler SW, Provost GS, Fieck A, Kretz PL, Bullock WO et al. 1991. Spectra of spontaneous and mutagen-induced mutations in the lacI gene in transgenic mice. PNAS 88:7958–62
    [Google Scholar]
  53. 53.
    Lanctot AA, Guo Y, Le Y, Edens BM, Nowakowski RS, Feng Y. 2017. Loss of Brap results in premature G1/S phase transition and impeded neural progenitor differentiation. Cell Rep 20:51148–60
    [Google Scholar]
  54. 54.
    Leibowitz BJ, Qiu W, Liu H, Cheng T, Zhang L, Yu J 2011. Uncoupling p53 functions in radiation-induced intestinal damage via PUMA and p21. Mol. Cancer Res. 9:5616–25
    [Google Scholar]
  55. 55.
    Li Y, Rao X, Tang P, Chen S, Guo Q et al. 2021. Bach2 deficiency promotes intestinal epithelial regeneration by accelerating DNA repair in intestinal stem cells. Stem Cell Rep 16:1120–33
    [Google Scholar]
  56. 56.
    Limoli CL, Giedzinski E, Rola R, Otsuka S, TD Palmer, Fike JR. 2004. Radiation response of neural precursor cells: linking cellular sensitivity to cell cycle checkpoints, apoptosis and oxidative stress. Radiat. Res. 161:117–27
    [Google Scholar]
  57. 57.
    Lopez Perez R, Brauer J, Rühle A, Trinh T, Sisombath S et al. 2019. Human mesenchymal stem cells are resistant to UV-B irradiation. Sci. Rep. 9:120000
    [Google Scholar]
  58. 58.
    Luo Y, Hartford SA, Zeng R, Southard TL, Shima N, Schimenti JC. 2014. Hypersensitivity of primordial germ cells to compromised replication-associated DNA repair involves ATM-p53-p21 signaling. PLOS Genet 10:7e1004471
    [Google Scholar]
  59. 59.
    Luo Y, Schimenti JC. 2015. MCM9 deficiency delays primordial germ cell proliferation independent of the ATM pathway. Genesis 53:11678–84
    [Google Scholar]
  60. 60.
    Lv F-J, Tuan RS, Cheung KMC, Leung VYL. 2014. Concise review: the surface markers and identity of human mesenchymal stem cells. Stem Cells 32:61408–19
    [Google Scholar]
  61. 61.
    Ma DK, Bonaguidi MA, Ming G-L, Song H. 2009. Adult neural stem cells in the mammalian central nervous system. Cell Res 19:6672–82
    [Google Scholar]
  62. 62.
    Mangale V, Marro BS, Plaisted WC, Walsh CM, Lane TE. 2017. Neural precursor cells derived from induced pluripotent stem cells exhibit reduced susceptibility to infection with a neurotropic coronavirus. Virology 511:49–55
    [Google Scholar]
  63. 63.
    Marin Navarro A, Pronk RJ, van der Geest AT, Oliynyk G, Nordgren A et al. 2020. p53 controls genomic stability and temporal differentiation of human neural stem cells and affects neural organization in human brain organoids. Cell Death Dis 11:152
    [Google Scholar]
  64. 64.
    Matsumura H, Mohri Y, Binh NT, Morinaga H, Fukuda M et al. 2016. Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis. Science 351:6273aad4395
    [Google Scholar]
  65. 65.
    McConnell MJ, Moran JV, Abyzov A, Akbarian S, Bae T et al. 2017. Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network. Science 356:6336eaal1641
    [Google Scholar]
  66. 66.
    McNairn AJ, Chuang C-H, Bloom JC, Wallace MD, Schimenti JC. 2019. Female-biased embryonic death from inflammation induced by genomic instability. Nature 567:7746105–8
    [Google Scholar]
  67. 67.
    Messiaen S, Le Bras A, Duquenne C, Barroca V, Moison D et al. 2013. Rad54 is required for the normal development of male and female germ cells and contributes to the maintainance of their genome integrity after genotoxic stress. Cell Death Dis 4:e774
    [Google Scholar]
  68. 68.
    Mgbemena VE, Signer RAJ, Wijayatunge R, Laxson T, Morrison SJ, Ross TS. 2017. Distinct Brca1 mutations differentially reduce hematopoietic stem cell function. Cell Rep 18:4947–60
    [Google Scholar]
  69. 69.
    Milholland B, Dong X, Zhang L, Hao X, Suh Y, Vijg J. 2017. Differences between germline and somatic mutation rates in humans and mice. Nat. Commun. 8:15183
    [Google Scholar]
  70. 70.
    Momcilovic O, Knobloch L, Fornsaglio J, Varum S, Easley C, Schatten G. 2010. DNA damage responses in human induced pluripotent stem cells and embryonic stem cells. PLOS ONE 5:10e13410
    [Google Scholar]
  71. 71.
    Moreira PI, Nunomura A, Nakamura M, Takeda A, Shenk JC et al. 2008. Nucleic acid oxidation in Alzheimer disease. Free Radic. . Biol. Med. 44:81493–505
    [Google Scholar]
  72. 72.
    Müller-Röver S, Handjiski B, van der Veen C, Eichmüller S, Foitzik K et al. 2001. A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages. J. Invest. Dermatol. 117:13–15
    [Google Scholar]
  73. 73.
    Nicolay NH, Lopez Perez R, Rühle A, Trinh T, Sisombath S et al. 2016. Mesenchymal stem cells maintain their defining stem cell characteristics after treatment with cisplatin. Sci. Rep. 6:20035
    [Google Scholar]
  74. 74.
    Nicolay NH, Rühle A, Perez RL, Trinh T, Sisombath S et al. 2016. Mesenchymal stem cells are sensitive to bleomycin treatment. Sci. Rep. 6:26645
    [Google Scholar]
  75. 75.
    Nicolay NH, Rühle A, Perez RL, Trinh T, Sisombath S et al. 2016. Mesenchymal stem cells exhibit resistance to topoisomerase inhibition. Cancer Lett 374:175–84
    [Google Scholar]
  76. 76.
    Nicolay NH, Sommer E, Lopez R, Wirkner U, Trinh T et al. 2013. Mesenchymal stem cells retain their defining stem cell characteristics after exposure to ionizing radiation. Int. J. Radiat. Oncol. Biol. Phys. 87:51171–78
    [Google Scholar]
  77. 77.
    Okae H, Toh H, Sato T, Hiura H, Takahashi S et al. 2018. Derivation of human trophoblast stem cells. Cell Stem Cell 22:150–63.e6
    [Google Scholar]
  78. 78.
    Orii KE, Lee Y, Kondo N, McKinnon PJ. 2006. Selective utilization of nonhomologous end-joining and homologous recombination DNA repair pathways during nervous system development. PNAS 103:2610017–22
    [Google Scholar]
  79. 79.
    Orvain C, Lin Y-L, Jean-Louis F, Hocini H, Hersant B et al. 2020. Hair follicle stem cell replication stress drives IFI16/STING-dependent inflammation in hidradenitis suppurativa. J. Clin. Invest. 130:73777–90
    [Google Scholar]
  80. 80.
    Panich U, Sittithumcharee G, Rathviboon N, Jirawatnotai S. 2016. Ultraviolet radiation-induced skin aging: the role of DNA damage and oxidative stress in epidermal stem cell damage mediated skin aging. Stem Cells Int 2016:7370642
    [Google Scholar]
  81. 81.
    Pech MF, Garbuzov A, Hasegawa K, Sukhwani M, Zhang RJ et al. 2015. High telomerase is a hallmark of undifferentiated spermatogonia and is required for maintenance of male germline stem cells. Genes Dev 29:232420–34
    [Google Scholar]
  82. 82.
    Pellegrinet L, Rodilla V, Liu Z, Chen S, Koch U et al. 2011. Dll1- and Dll4-mediated Notch signaling are required for homeostasis of intestinal stem cells. Gastroenterology 140:41230–40.e1
    [Google Scholar]
  83. 83.
    Pilzecker B, Buoninfante OA, van den Berk P, Lancini C, Song J-Y et al. 2017. DNA damage tolerance in hematopoietic stem and progenitor cells in mice. PNAS 114:33E6875–83
    [Google Scholar]
  84. 84.
    Ponti G, Obernier K, Alvarez-Buylla A. 2013. Lineage progression from stem cells to new neurons in the adult brain ventricular-subventricular zone. Cell Cycle 12:111649–50
    [Google Scholar]
  85. 85.
    Powell AE, Wang Y, Li Y, Poulin EJ, Means AL et al. 2012. The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor. Cell 149:1146–58
    [Google Scholar]
  86. 86.
    Qanash H, Linask K, Beers J, Zou J, Larochelle A. 2018. Generation of Fanconi anemia iPSC clones by addition of a small molecule inhibitor of p53 during reprogramming. Blood 132:Suppl. 13857
    [Google Scholar]
  87. 87.
    Reese JS, Liu L, Gerson SL. 2003. Repopulating defect of mismatch repair-deficient hematopoietic stem cells. Blood 102:51626–33
    [Google Scholar]
  88. 88.
    Rodier F, Coppé J-P, Patil CK, Hoeijmakers WAM, Muñoz DP et al. 2009. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat. Cell Biol. 11:8973–79
    [Google Scholar]
  89. 89.
    Rossi DJ, Bryder D, Seita J, Nussenzweig A, Hoeijmakers J, Weissman IL. 2007. Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature 447:7145725–29
    [Google Scholar]
  90. 90.
    Rouhani FJ, Nik-Zainal S, Wuster A, Li Y, Conte N et al. 2016. Mutational history of a human cell lineage from somatic to induced pluripotent stem cells. PLOS Genet 12:4e1005932
    [Google Scholar]
  91. 91.
    Rübe CE, Fricke A, Widmann TA, Fürst T, Madry H et al. 2011. Accumulation of DNA damage in hematopoietic stem and progenitor cells during human aging. PLOS ONE 6:3e17487
    [Google Scholar]
  92. 92.
    Rühle A, Xia O, Perez RL, Trinh T, Richter W et al. 2018. The radiation resistance of human multipotent mesenchymal stromal cells is independent of their tissue of origin. Int. J. Radiat. Oncol. Biol. Phys. 100:51259–69
    [Google Scholar]
  93. 93.
    Ruiz S, Lopez-Contreras AJ, Gabut M, Marion RM, Gutierrez-Martinez P et al. 2015. Limiting replication stress during somatic cell reprogramming reduces genomic instability in induced pluripotent stem cells. Nat. Commun. 6:8036
    [Google Scholar]
  94. 94.
    Ruiz S, Panopoulos AD, Herrerías A, Bissig K-D, Lutz M et al. 2011. A high proliferation rate is required for cell reprogramming and maintenance of human embryonic stem cell identity. Curr. Biol. 21:145–52
    [Google Scholar]
  95. 95.
    Sacco R, Tamblyn L, Rajakulendran N, Bralha FN, Tropepe V, Laposa RR. 2013. Cockayne syndrome b maintains neural precursor function. DNA Repair 12:2110–20
    [Google Scholar]
  96. 96.
    Schmitt MW, Kennedy SR, Salk JJ, Fox EJ, Hiatt JB, Loeb LA. 2012. Detection of ultra-rare mutations by next-generation sequencing. PNAS 109:3614508–13
    [Google Scholar]
  97. 97.
    Schuler N, Rübe CE. 2013. Accumulation of DNA damage-induced chromatin alterations in tissue-specific stem cells: the driving force of aging?. PLOS ONE 8:5e63932
    [Google Scholar]
  98. 98.
    Seldin L, Macara IG. 2020. DNA damage promotes epithelial hyperplasia and fate mis-specification via fibroblast inflammasome activation. Dev. Cell 55:5558–73.e6
    [Google Scholar]
  99. 99.
    Serrano L, Liang L, Chang Y, Deng L, Maulion C et al. 2011. Homologous recombination conserves DNA sequence integrity throughout the cell cycle in embryonic stem cells. Stem Cells Dev 20:2363–74
    [Google Scholar]
  100. 100.
    Shen X, Wang R, Kim MJ, Hu Q, Hsu C-C et al. 2020. A surge of DNA damage links transcriptional reprogramming and hematopoietic deficit in Fanconi anemia. Mol. Cell 80:61013–24.e6
    [Google Scholar]
  101. 101.
    Shin W, Alpaugh W, Hallihan LJ, Sinha S, Crowther E et al. 2021. PNKP is required for maintaining the integrity of progenitor cell populations in adult mice. Life Sci. Alliance 4:9e202000790
    [Google Scholar]
  102. 102.
    Shook BA, Manz DH, Peters JJ, Kang S, Conover JC. 2012. Spatiotemporal changes to the subventricular zone stem cell pool through aging. J. Neurosci. 32:206947–56
    [Google Scholar]
  103. 103.
    Siegl-Cachedenier I, Flores I, Klatt P, Blasco MA. 2007. Telomerase reverses epidermal hair follicle stem cell defects and loss of long-term survival associated with critically short telomeres. J. Cell Biol. 179:2277–90
    [Google Scholar]
  104. 104.
    Sii-Felice K, Barroca V, Etienne O, Riou L, Hoffschir F et al. 2008. Role of Fanconi DNA repair pathway in neural stem cell homeostasis. Cell Cycle 7:131911–15
    [Google Scholar]
  105. 105.
    Sii-Felice K, Etienne O, Hoffschir F, Mathieu C, Riou L et al. 2008. Fanconi DNA repair pathway is required for survival and long-term maintenance of neural progenitors. EMBO J 27:5770–81
    [Google Scholar]
  106. 106.
    Singh VP, McKinney S, Gerton JL. 2020. Persistent DNA damage and senescence in the placenta impacts developmental outcomes of embryos. Dev. Cell 54:3333–47.e7
    [Google Scholar]
  107. 107.
    Sotiropoulou PA, Candi A, Mascré G, De Clercq S, Youssef KK et al. 2010. Bcl-2 and accelerated DNA repair mediates resistance of hair follicle bulge stem cells to DNA-damage-induced cell death. Nat. Cell Biol. 12:6572–82
    [Google Scholar]
  108. 108.
    Sotiropoulou PA, Karambelas AE, Debaugnies M, Candi A, Bouwman P et al. 2013. BRCA1 deficiency in skin epidermis leads to selective loss of hair follicle stem cells and their progeny. Genes Dev 27:139–51
    [Google Scholar]
  109. 109.
    Stambrook PJ, Tichy ED. 2010. Preservation of genomic integrity in mouse embryonic stem cells. Adv. Exp. Med. Biol. 695:59–75
    [Google Scholar]
  110. 110.
    Sun Y, Pollard S, Conti L, Toselli M, Biella G et al. 2008. Long-term tripotent differentiation capacity of human neural stem (NS) cells in adherent culture. Mol. Cell. Neurosci. 38:2245–58
    [Google Scholar]
  111. 111.
    Sykora P, Yang J-L, Ferrarelli LK, Tian J, Tadokoro T et al. 2013. Modulation of DNA base excision repair during neuronal differentiation. Neurobiol. Aging 34:71717–27
    [Google Scholar]
  112. 112.
    Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T et al. 2007. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:5861–72
    [Google Scholar]
  113. 113.
    Takahashi K, Yamanaka S. 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:4663–76
    [Google Scholar]
  114. 114.
    Takeda N, Jain R, LeBoeuf MR, Wang Q, Lu MM, Epstein JA. 2011. Interconversion between intestinal stem cell populations in distinct niches. Science 334:60611420–24
    [Google Scholar]
  115. 115.
    Tam PP, Snow MH. 1981. Proliferation and migration of primordial germ cells during compensatory growth in mouse embryos. J. Embryol. Exp. Morphol. 64:133–47
    [Google Scholar]
  116. 116.
    Tanaka S, Kunath T, Hadjantonakis AK, Nagy A, Rossant J. 1998. Promotion of trophoblast stem cell proliferation by FGF4. Science 282:53962072–75
    [Google Scholar]
  117. 117.
    Tesar PJ, Chenoweth JG, Brook FA, Davies TJ, Evans EP et al. 2007. New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature 448:7150196–99
    [Google Scholar]
  118. 118.
    Tian H, Biehs B, Warming S, Leong KG, Rangell L et al. 2011. A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature 478:7368255–59
    [Google Scholar]
  119. 119.
    Tichy ED, Liang L, Deng L, Tischfield J, Schwemberger S et al. 2011. Mismatch and base excision repair proficiency in murine embryonic stem cells. DNA Repair 10:4445–51
    [Google Scholar]
  120. 120.
    Tichy ED, Pillai R, Deng L, Liang L, Tischfield J et al. 2010. Mouse embryonic stem cells, but not somatic cells, predominantly use homologous recombination to repair double-strand DNA breaks. Stem Cells Dev 19:111699–711
    [Google Scholar]
  121. 121.
    Tichy ED, Pillai R, Deng L, Tischfield JA, Hexley P et al. 2012. The abundance of Rad51 protein in mouse embryonic stem cells is regulated at multiple levels. Stem Cell Res 9:2124–34
    [Google Scholar]
  122. 122.
    Tropepe V, Sibilia M, Ciruna BG, Rossant J, Wagner EF, van der Kooy D. 1999. Distinct neural stem cells proliferate in response to EGF and FGF in the developing mouse telencephalon. Dev. Biol. 208:1166–88
    [Google Scholar]
  123. 123.
    Trushina E, McMurray CT. 2007. Oxidative stress and mitochondrial dysfunction in neurodegenerative diseases. Neuroscience 145:41233–48
    [Google Scholar]
  124. 124.
    Uccelli A, Moretta L, Pistoia V. 2008. Mesenchymal stem cells in health and disease. Nat. Rev. Immunol. 8:9726–36
    [Google Scholar]
  125. 125.
    van der Flier LG, Haegebarth A, Stange DE, van de Wetering M, Clevers H. 2009. OLFM4 is a robust marker for stem cells in human intestine and marks a subset of colorectal cancer cells. Gastroenterology 137:115–17
    [Google Scholar]
  126. 126.
    van der Flier LG, van Gijn ME, Hatzis P, Kujala P, Haegebarth A et al. 2009. Transcription factor Achaete scute-like 2 controls intestinal stem cell fate. Cell 136:5903–12
    [Google Scholar]
  127. 127.
    van der Laan S, Tsanov N, Crozet C, Maiorano D. 2013. High Dub3 expression in mouse ESCs couples the G1/S checkpoint to pluripotency. Mol. Cell 52:3366–79
    [Google Scholar]
  128. 128.
    Wang J, Sun Q, Morita Y, Jiang H, Gross A et al. 2012. A differentiation checkpoint limits hematopoietic stem cell self-renewal in response to DNA damage. Cell 148:51001–14
    [Google Scholar]
  129. 129.
    Wang R, Li H, Wu J, Cai Z-Y, Li B et al. 2020. Gut stem cell necroptosis by genome instability triggers bowel inflammation. Nature 580:7803386–90
    [Google Scholar]
  130. 130.
    Watanabe K, Ikuno Y, Kakeya Y, Ikeno S, Taniura H et al. 2019. Age-related dysfunction of the DNA damage response in intestinal stem cells. Inflamm. Regen. 39:8
    [Google Scholar]
  131. 131.
    Weiss S, Dunne C, Hewson J, Wohl C, Wheatley M et al. 1996. Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis. J. Neurosci. 16:237599–609
    [Google Scholar]
  132. 132.
    Wognum AW, Eaves AC, Thomas TE. 2003. Identification and isolation of hematopoietic stem cells. Arch. Med. Res. 34:6461–75
    [Google Scholar]
  133. 133.
    Yang J-L, Weissman L, Bohr VA, Mattson MP. 2008. Mitochondrial DNA damage and repair in neurodegenerative disorders. DNA Repair 7:71110–20
    [Google Scholar]
  134. 134.
    Young MA, Larson DE, Sun C-W, George DR, Ding L et al. 2012. Background mutations in parental cells account for most of the genetic heterogeneity of induced pluripotent stem cells. Cell Stem Cell 10:5570–82
    [Google Scholar]
  135. 135.
    Zhao B, Zhang W-D, Duan Y-L, Lu Y-Q, Cun Y-X et al. 2015. Filia is an ESC-specific regulator of DNA damage response and safeguards genomic stability. Cell Stem Cell 16:6684–98
    [Google Scholar]
/content/journals/10.1146/annurev-genet-072920-022154
Loading
/content/journals/10.1146/annurev-genet-072920-022154
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error