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Epigenetics in Stem Cell Biology

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Regenerative Medicine and Stem Cell Biology

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Abstract

Epigenetics is the field of study concerned with alterations in gene expression which occur without changes to an organism’s DNA sequence. Epigenetic modifications include histone modifications, DNA methylation, and interactions with non-coding RNAs. In this chapter, you will learn how epigenetic modifications control the development, proliferation, and self-renewal of stem cells, and how these modifications also play important roles in cell fate decisions such as differentiation, de-differentiation, and transdifferentiation. The chapter covers epigenetic control of reprogramming of stem cells, in the generation of induced pluripotent cells, and in understanding the origins of Cancer Stem Cells (CSCs). The chapter covers the environmental factors that influence stem cell biology and aging and interact strongly with epigenetic control mechanisms. The chapter concludes with understanding these control mechanisms, and the impact of epigenetics on stem cell development, senescence, and regenerative capacity and their role in developing epigenetic-based therapeutics.

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References

  1. Holliday R. Epigenetics: an overview. Dev Genet. 1994;15(6):453–7.

    Article  CAS  PubMed  Google Scholar 

  2. Wu C, Morris JR. Genes, genetics, and epigenetics: a correspondence. Science. 2001;293(5532):1103–5.

    Article  CAS  Google Scholar 

  3. Holliday R. The inheritance of epigenetic defects. Science. 1987;238(4824):163–70.

    Article  CAS  PubMed  Google Scholar 

  4. Glaros S, et al. The reversible epigenetic silencing of BRM: implications for clinical targeted therapy. Oncogene. 2007;26(49):7058–66.

    Article  CAS  PubMed  Google Scholar 

  5. Doskočil J, Šorm F. Distribution of 5-methylcytosine in pyrimidine sequences of deoxyribonucleic acids. Biochim Biophys Acta. 1962;55(6):953–9.

    Article  PubMed  Google Scholar 

  6. Wyatt GR. Recognition and estimation of 5-methylcytosine in nucleic acids. Biochem J. 1951;48(5):581–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hotchkiss RD. The quantitative separation of purines, pyrimidines, and nucleosides by paper chromatography. J Biol Chem. 1948;175(1):315–32.

    CAS  PubMed  Google Scholar 

  8. Saxonov S, Berg P, Brutlag DL. A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc Natl Acad Sci. 2006;103(5):1412–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Goyal R, Reinhardt R, Jeltsch A. Accuracy of DNA methylation pattern preservation by the Dnmt1 methyltransferase. Nucleic Acids Res. 2006;34(4):1182–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Okano M, Xie S, Li E. Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet. 1998;19(3):219–20.

    Article  CAS  PubMed  Google Scholar 

  11. Aapola U, et al. Isolation and initial characterization of a novel zinc finger gene, DNMT3L, on 21q22.3, related to the cytosine-5-methyltransferase 3 gene family. Genomics. 2000;65(3):293–8.

    Article  CAS  PubMed  Google Scholar 

  12. Suetake I, et al. DNMT3L stimulates the DNA methylation activity of Dnmt3a and Dnmt3b through a direct interaction. J Biol Chem. 2004;279(26):27816–23.

    Article  CAS  PubMed  Google Scholar 

  13. Gowher H, et al. Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L. J Biol Chem. 2005;280(14):13341–8.

    Article  CAS  PubMed  Google Scholar 

  14. Goll MG, et al. Methylation of tRNAAsp by the DNA Methyltransferase Homolog Dnmt2. Science. 2006;311(5759):395.

    Article  CAS  PubMed  Google Scholar 

  15. Bogdanović O, et al. Active DNA demethylation at enhancers during the vertebrate phylotypic period. Nat Genet. 2016;48(4):417–26.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Tahiliani M, et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324(5929):930–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sen M, et al. Strand-specific single-cell methylomics reveals distinct modes of DNA demethylation dynamics during early mammalian development. bioRxiv. 2019:804526.

    Google Scholar 

  18. Jiang C, Pugh BF. Nucleosome positioning and gene regulation: advances through genomics. Nat Rev Genet. 2009;10(3):161–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res. 2011;21(3):381–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Costello KR, Schones DE. Chromatin modifications in metabolic disease: Potential mediators of long-term disease risk. Wiley Interdiscip Rev Syst Biol Med. 2018;10(4):e1416.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Jiang J, et al. Investigation of the acetylation mechanism by GCN5 histone acetyltransferase. PLoS One. 2012;7(5):e36660.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Dutnall RN, et al. Structure of the histone acetyltransferase Hat1: a paradigm for the GCN5-Related N-acetyltransferase superfamily. Cell. 1998;94(4):427–38.

    Article  CAS  PubMed  Google Scholar 

  23. Lee DY, et al. A positive role for histone acetylation in transcription factor access to nucleosomal DNA. Cell. 1993;72(1):73–84.

    Article  CAS  PubMed  Google Scholar 

  24. Garcia-Ramirez M, Rocchini C, Ausio J. Modulation of chromatin folding by histone acetylation. J Biol Chem. 1995;270(30):17923–8.

    Article  CAS  PubMed  Google Scholar 

  25. Lee J, Lee T-H. How protein binding sensitizes the nucleosome to histone H3K56 acetylation. ACS Chem Biol. 2019;14(3):506–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Greer EL, Shi Y. Histone methylation: a dynamic mark in health, disease and inheritance. Nat Rev Genet. 2012;13(5):343–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Campagna-Slater V, et al. Structural chemistry of the histone methyltransferases cofactor binding site. J Chem Inf Model. 2011;51(3):612–23.

    Article  CAS  PubMed  Google Scholar 

  28. Lu D. Epigenetic modification enzymes: catalytic mechanisms and inhibitors. Acta Pharm Sin B. 2013;3(3):141–9.

    Article  Google Scholar 

  29. Krogan NJ, et al. The Paf1 Complex Is Required for Histone H3 Methylation by COMPASS and Dot1p: Linking Transcriptional Elongation to Histone Methylation. Mol Cell. 2003;11(3):721–9.

    Article  CAS  PubMed  Google Scholar 

  30. Krogan NJ, et al. Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is linked to transcriptional elongation by RNA polymerase II. Mol Cell Biol. 2003;23(12):4207–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Cao R, et al. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science. 2002;298(5595):1039–43.

    Article  CAS  PubMed  Google Scholar 

  32. Nakayama J, et al. Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science. 2001;292(5514):110–3.

    Article  CAS  PubMed  Google Scholar 

  33. Kooistra SM, Helin K. Molecular mechanisms and potential functions of histone demethylases. Nat Rev Mol Cell Biol. 2012;13(5):297–311.

    Article  CAS  PubMed  Google Scholar 

  34. Rossetto D, Avvakumov N, Côté J. Histone phosphorylation: a chromatin modification involved in diverse nuclear events. Epigenetics. 2012;7(10):1098–108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Lo WS, et al. Phosphorylation of serine 10 in histone H3 is functionally linked in vitro and in vivo to Gcn5-mediated acetylation at lysine 14. Mol Cell. 2000;5(6):917–26.

    Article  CAS  PubMed  Google Scholar 

  36. Cao J, Yan Q. Histone ubiquitination and deubiquitination in transcription, DNA damage response, and cancer. Front Oncol. 2012;2:26.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Shiio Y, Eisenman RN. Histone sumoylation is associated with transcriptional repression. Proc Natl Acad Sci. 2003;100(23):13225.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Esteller M. Non-coding RNAs in human disease. Nat Rev Genet. 2011;12(12):861–74.

    Article  CAS  PubMed  Google Scholar 

  39. Zaratiegui M, Irvine DV, Martienssen RA. Noncoding RNAs and Gene Silencing. Cell. 2007;128(4):763–76.

    Article  CAS  PubMed  Google Scholar 

  40. Bhan A, Mandal SS. Long Noncoding RNAs: Emerging Stars in Gene Regulation, Epigenetics and Human Disease. ChemMedChem. 2014;9(9):1932–56.

    Article  CAS  PubMed  Google Scholar 

  41. Waddington CH. The epigenotype. Endeavour. 1942;1:18–20.

    Google Scholar 

  42. Waddington C. The strategy of the genes: a discussion of some aspects of theoretical biology. London: Allen & Unwin; 1957.

    Google Scholar 

  43. Weinberger L, et al. Dynamic stem cell states: naive to primed pluripotency in rodents and humans. Nat Rev Mol Cell Biol. 2016;17(3):155–69.

    Article  CAS  PubMed  Google Scholar 

  44. Falls JG, et al. Genomic imprinting: implications for human disease. Am J Pathol. 1999;154(3):635–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Riso V, et al. ZFP57 maintains the parent-of-origin-specific expression of the imprinted genes and differentially affects non-imprinted targets in mouse embryonic stem cells. Nucleic Acids Res. 2016;44(17):8165–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Atlasi Y, Stunnenberg HG. The interplay of epigenetic marks during stem cell differentiation and development. Nat Rev Genet. 2017;18(11):643–58.

    Article  CAS  PubMed  Google Scholar 

  47. Takahashi K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861–72.

    Article  CAS  PubMed  Google Scholar 

  48. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–76.

    Article  CAS  PubMed  Google Scholar 

  49. Hawkins RD, et al. Distinct epigenomic landscapes of pluripotent and lineage-committed human cells. Cell Stem Cell. 2010;6(5):479–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Chen J, et al. H3K9 methylation is a barrier during somatic cell reprogramming into iPSCs. Nat Genet. 2013;45(1):34–42.

    Article  CAS  PubMed  Google Scholar 

  51. Nishino K, et al. Defining hypo-methylated regions of stem cell-specific promoters in human iPS cells derived from extra-embryonic amnions and lung fibroblasts. PLoS One. 2010;5(9):e13017.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Pawlak M, Jaenisch R. De novo DNA methylation by Dnmt3a and Dnmt3b is dispensable for nuclear reprogramming of somatic cells to a pluripotent state. Genes Dev. 2011;25(10):1035–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Mikkelsen TS, et al. Dissecting direct reprogramming through integrative genomic analysis. Nature. 2008;454(7200):49–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Doege CA, et al. Early-stage epigenetic modification during somatic cell reprogramming by Parp1 and Tet2. Nature. 2012;488(7413):652–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Wang T, et al. Subtelomeric hotspots of aberrant 5-hydroxymethylcytosine-mediated epigenetic modifications during reprogramming to pluripotency. Nat Cell Biol. 2013;15(6):700–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Judson RL, et al. Embryonic stem cell–specific microRNAs promote induced pluripotency. Nat Biotechnol. 2009;27(5):459–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Li Z, et al. Small RNA-mediated regulation of iPS cell generation. EMBO J. 2011;30(5):823–34.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Loewer S, et al. Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nat Genet. 2010;42(12):1113–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Maherali N, et al. Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell. 2007;1(1):55–70.

    Article  CAS  PubMed  Google Scholar 

  60. Pasque V, et al. Histone variant macroH2A marks embryonic differentiation in vivo and acts as an epigenetic barrier to induced pluripotency. J Cell Sci. 2012;125(Pt 24):6094–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Bernstein BE, et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell. 2006;125(2):315–26.

    Article  CAS  PubMed  Google Scholar 

  62. Wen B, et al. Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells. Nat Genet. 2009;41(2):246–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Atkinson S, Armstrong L. Epigenetics in embryonic stem cells: regulation of pluripotency and differentiation. Cell Tissue Res. 2008;331(1):23–9.

    Article  PubMed  Google Scholar 

  64. Kimura H, et al. Histone code modifications on pluripotential nuclei of reprogrammed somatic cells. Mol Cell Biol. 2004;24(13):5710–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Lee JH, Hart SR, Skalnik DG. Histone deacetylase activity is required for embryonic stem cell differentiation. Genesis. 2004;38(1):32–8.

    Article  CAS  PubMed  Google Scholar 

  66. Huang B, Li G, Jiang XH. Fate determination in mesenchymal stem cells: a perspective from histone-modifying enzymes. Stem Cell Res Ther. 2015;6(1):35.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Okada T, Okada T. Transdifferentiation: flexibility in cell differentiation: Oxford University Press on Demand; 1991.

    Google Scholar 

  68. Cho YD, et al. Epigenetic modifications and canonical wingless/int-1 class (WNT) signaling enable trans-differentiation of nonosteogenic cells into osteoblasts. J Biol Chem. 2014;289(29):20120–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Dhawan S, et al. Pancreatic beta cell identity is maintained by DNA methylation-mediated repression of Arx. Dev Cell. 2011;20(4):419–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Oh J, Lee YD, Wagers AJ. Stem cell aging: mechanisms, regulators and therapeutic opportunities. Nat Med. 2014;20(8):870–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Ahmed ASI, et al. Effect of aging on stem cells. World J Exp Med. 2017;7(1):1–10.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Sun D, et al. Epigenomic profiling of young and aged HSCs reveals concerted changes during aging that reinforce self-renewal. Cell Stem Cell. 2014;14(5):673–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Cho RH, Sieburg HB, Muller-Sieburg CE. A new mechanism for the aging of hematopoietic stem cells: aging changes the clonal composition of the stem cell compartment but not individual stem cells. Blood. 2008;111(12):5553–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Chambers SM, et al. Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation. PLoS Biol. 2007;5(8):e201.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Liu L, et al. Chromatin modifications as determinants of muscle stem cell quiescence and chronological aging. Cell Rep. 2013;4(1):189–204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Li J, et al. Age-specific functional epigenetic changes in p21 and p16 in injury-activated satellite cells. Stem Cells. 2015;33(3):951–61.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Schwörer S, et al. Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals. Nature. 2016;540(7633):428–32.

    Article  PubMed  CAS  Google Scholar 

  78. Li Z, et al. Epigenetic dysregulation in mesenchymal stem cell aging and spontaneous differentiation. PLoS One. 2011;6(6):e20526.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Harvey A, et al. Interplay between metabolites and the epigenome in regulating embryonic and adult stem cell potency and maintenance. Stem Cell Rep. 2019;13(4):573–89.

    Article  CAS  Google Scholar 

  80. Wang J, et al. Dependence of mouse embryonic stem cells on threonine catabolism. Science. 2009;325(5939):435–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Shyh-Chang N, et al. Influence of threonine metabolism on S-adenosylmethionine and histone methylation. Science. 2013;339(6116):222–6.

    Article  PubMed  CAS  Google Scholar 

  82. Moussaieff A, et al. Glycolysis-mediated changes in acetyl-CoA and histone acetylation control the early differentiation of embryonic stem cells. Cell Metab. 2015;21(3):392–402.

    Article  CAS  PubMed  Google Scholar 

  83. Carey BW, et al. Intracellular alpha-ketoglutarate maintains the pluripotency of embryonic stem cells. Nature. 2015;518(7539):413–6.

    Article  CAS  PubMed  Google Scholar 

  84. Mali P, et al. Butyrate greatly enhances derivation of human induced pluripotent stem cells by promoting epigenetic remodeling and the expression of pluripotency-associated genes. Stem Cells. 2010;28(4):713–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Singh N, et al. Blockade of dendritic cell development by bacterial fermentation products butyrate and propionate through a transporter (Slc5a8)-dependent inhibition of histone deacetylases. J Biol Chem. 2010;285(36):27601–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Downing TL, et al. Biophysical regulation of epigenetic state and cell reprogramming. Nat Mater. 2013;12(12):1154–62.

    Article  CAS  PubMed  Google Scholar 

  87. Illi B, et al. Epigenetic histone modification and cardiovascular lineage programming in mouse embryonic stem cells exposed to laminar shear stress. Circ Res. 2005;96(5):501–8.

    Article  CAS  PubMed  Google Scholar 

  88. Yu Z, et al. Cancer stem cells. Int J Biochem Cell Biol. 2012;44(12):2144–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Tominaga K, et al. Semaphorin signaling via MICAL3 induces symmetric cell division to expand breast cancer stem-like cells. Proc Natl Acad Sci. 2019;116(2):625.

    Article  CAS  PubMed  Google Scholar 

  90. Plaks V, Kong N, Werb Z. The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells? Cell Stem Cell. 2015;16(3):225–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Conheim J. Congenitales, quergestreiftes muskelsarkon der nireren. Virchows Arch. 1875;65:64.

    Article  Google Scholar 

  92. Virchow RLK. Die krankhaften geschwülste, vol. 3: Verlag von August Hirschwald; 1867.

    Google Scholar 

  93. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3(7):730–7.

    Article  CAS  PubMed  Google Scholar 

  94. Toh TB, Lim JJ, Chow EK-H. Epigenetics in cancer stem cells. Mol Cancer. 2017;16(1):29.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Hoffmeyer K, et al. Wnt/β-catenin signaling regulates telomerase in stem cells and cancer cells. Science. 2012;336(6088):1549–54.

    Article  CAS  PubMed  Google Scholar 

  96. D’Angelo RC, et al. Notch reporter activity in breast cancer cell lines identifies a subset of cells with stem cell activity. Mol Cancer Ther. 2015;14(3):779–87.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Wang Z, et al. Notch signaling drives stemness and tumorigenicity of esophageal adenocarcinoma. Cancer Res. 2014;74(21):6364–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Li E, et al. Sonic hedgehog pathway mediates genistein inhibition of renal cancer stem cells. Oncol Lett. 2019;18(3):3081–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Koinuma K, et al. Epigenetic silencing of AXIN2 in colorectal carcinoma with microsatellite instability. Oncogene. 2006;25(1):139–46.

    Article  CAS  PubMed  Google Scholar 

  100. Suzuki H, et al. Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat Genet. 2004;36(4):417–22.

    Article  CAS  PubMed  Google Scholar 

  101. Hussain M, et al. Tobacco smoke induces polycomb-mediated repression of Dickkopf-1 in lung cancer cells. Cancer Res. 2009;69(8):3570.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Biegel JA, et al. Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res. 1999;59(1):74.

    CAS  PubMed  Google Scholar 

  103. Versteege I, et al. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature. 1998;394(6689):203–6.

    Article  CAS  PubMed  Google Scholar 

  104. Sévenet N, et al. Constitutional mutations of the hSNF5/INI1 gene predispose to a variety of cancers. Am J Hum Genet. 1999;65(5):1342–8.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Canettieri G, et al. Histone deacetylase and Cullin3–RENKCTD11 ubiquitin ligase interplay regulates Hedgehog signalling through Gli acetylation. Nat Cell Biol. 2010;12(2):132–42.

    Article  CAS  PubMed  Google Scholar 

  106. Di Marcotullio L, et al. REN(KCTD11) is a suppressor of Hedgehog signaling and is deleted in human medulloblastoma. Proc Natl Acad Sci U S A. 2004;101(29):10833–8.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Jin L, Vu TT, Datta PK. STRAP mediates the stemness of human colorectal cancer cells by epigenetic regulation of Notch pathway: AACR; 2016.

    Google Scholar 

  108. Ghoshal P, et al. Loss of the SMRT/NCoR2 corepressor correlates with JAG2 overexpression in multiple myeloma. Cancer Res. 2009;69(10):4380–7.

    Article  CAS  PubMed  Google Scholar 

  109. El-Badawy A, et al. Telomerase reverse transcriptase coordinates with the epithelial-to-mesenchymal transition through a feedback loop to define properties of breast cancer stem cells. Biology Open. 2018;7(7):034181.

    Article  CAS  Google Scholar 

  110. Korpal M, et al. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem. 2008;283(22):14910–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Cao Q, et al. Repression of E-cadherin by the polycomb group protein EZH2 in cancer. Oncogene. 2008;27(58):7274–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Koizume S, et al. Heterogeneity in the modification and involvement of chromatin components of the CpG island of the silenced human CDH1 gene in cancer cells. Nucleic Acids Res. 2002;30(21):4770–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Tellez CS, et al. EMT and stem cell-like properties associated with miR-205 and miR-200 epigenetic silencing are early manifestations during carcinogen-induced transformation of human lung epithelial cells. Cancer Res. 2011;71(8):3087–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. To KK, et al. Histone modifications at the ABCG2 promoter following treatment with histone deacetylase inhibitor mirror those in multidrug-resistant cells. Mol Cancer Res. 2008;6(1):151–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. An Y, Ongkeko WM. ABCG2: the key to chemoresistance in cancer stem cells? Expert Opin Drug Metab Toxicol. 2009;5(12):1529–42.

    Article  CAS  PubMed  Google Scholar 

  116. Krivtsov AV, et al. Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature. 2006;442(7104):818–22.

    Article  CAS  PubMed  Google Scholar 

  117. Smith L-L, et al. Functional crosstalk between Bmi1 and MLL/Hoxa9 axis in establishment of normal hematopoietic and leukemic stem cells. Cell Stem Cell. 2011;8(6):649–62.

    Article  CAS  PubMed  Google Scholar 

  118. Ley TJ, et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368(22):2059–74.

    Article  PubMed  CAS  Google Scholar 

  119. Wang Y, et al. Epigenetic targeting of ovarian cancer stem cells. Cancer Res. 2014;74(17):4922–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Liu CC, et al. IL-6 enriched lung cancer stem-like cell population by inhibition of cell cycle regulators via DNMT1 upregulation. Int J Cancer. 2015;136(3):547–59.

    CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by ASRT JESOR grant # 5275, from the Egyptian Academy of Scientific Research and Technology (ASRT), and by internal funding from Zewail City of Science and Technology (ZC 003-2019).

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Authors and Affiliations

  1. Center of Excellence for Stem Cells and Regenerative Medicine (CESC), Helmy Institute of Biomedical Sciences, Zewail City of Science and Technology, Giza, Egypt

    Mohamed A. Nasr, Tasneem Abed, Azza M. El-Derby & Nagwa El-Badri

  2. Biomedical Sciences, University of Science and Technology, Zewail City of Science and Technology, Giza, Egypt

    Mohamed Medhat Ali

  3. Department of Medical Microbiology and Immunology, Faculty of Medicine, Mansoura University, Mansoura, Egypt

    Mohamed Medhat Ali

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  1. Mohamed A. Nasr
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Correspondence to Nagwa El-Badri .

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    Nagwa El-Badri

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Nasr, M.A., Abed, T., El-Derby, A.M., Ali, M.M., El-Badri, N. (2020). Epigenetics in Stem Cell Biology. In: El-Badri, N. (eds) Regenerative Medicine and Stem Cell Biology . Learning Materials in Biosciences. Springer, Cham. https://doi.org/10.1007/978-3-030-55359-3_7

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