Stem cell plasticity in development and cancer: Epigenetic origin of cancer stem cells

Subcellular Biochemistry

Volumn 61, Issue , 2013, Pages 545-565

  Shah, Mansi ^a   Allegrucci, Cinzia ^a,b  

^a UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^b UNIVERSITY OF NOTTINGHAM   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ADULT STEM CELL; ANIMAL; CANCER STEM CELL; CELL DIFFERENTIATION; CELL LINEAGE; CELL PROLIFERATION; CELL TRANSFORMATION; EMBRYONIC STEM CELL; GENE EXPRESSION REGULATION; GENETIC EPIGENESIS; GENETICS; HUMAN; METABOLISM; NEOPLASM; NUCLEAR REPROGRAMMING; PATHOLOGY; REVIEW;

ADULT STEM CELLS; ANIMALS; CELL DIFFERENTIATION; CELL LINEAGE; CELL PROLIFERATION; CELL TRANSFORMATION, NEOPLASTIC; EMBRYONIC STEM CELLS; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; NEOPLASMS; NEOPLASTIC STEM CELLS; NUCLEAR REPROGRAMMING;

EID: 84890859807     PISSN: 03060225     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-94-007-4525-4_24     Document Type: Article

References (118)

1. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100: 3983-3988.
2. Allegrucci C, Thurston A, Lucas E, Young L (2005) Epigenetics and the germline. Reproduction 129: 137-149.
3. Allegrucci C, Wu YZ, Thurston A, Denning CN, Priddle H, Mummery CL, Ward-van Oostwaard D, Andrews PW, Stojkovic M, Smith N, Parkin T, Jones ME, Warren G, Yu L, Brena RM, Plass C, Young LE (2007) Restriction landmark genome scanning identifies culture-induced DNA methylation instability in the human embryonic stem cell epigenome. Hum Mol Genet 16: 1253-1268.
4. Allegrucci C, Rushton MD, Dixon JE, Sottile V, Shah M, Kumari R, Watson S, Alberio R, Johnson AD (2011) Epigenetic reprogramming of breast cancer cells with oocyte extracts. Mol Cancer 10: 7.
5. Asp P, Blum R, Vethantham V, Parisi F, Micsinai M, Cheng J, Bowman C, Kluger Y, Dynlacht BD (2011) PNAS Plus: genome-wide remodeling of the epigenetic landscape during myogenic differentiation. Proc Natl Acad Sci USA 108: E149-E158.
6. Ball MP, Li JB, Gao Y, Lee J-H, LeProust EM, Park I-H, Xie B, Daley GQ, Church GM (2009) Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells. Nat Biotechnol 27: 361-368.
7. Bapat SA, Mali AM, Koppikar CB, Kurrey NK (2005) Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer. Cancer Res 65: 3025-3029.
8. Barrero MJ, Boue S, Izpisua Belmonte JC (2010) Epigenetic mechanisms that regulate cell identity. Cell Stem Cell 7: 565-570.
9. Baylin SB, Ohm JE (2006) Epigenetic gene silencing in cancer-a mechanism for early oncogenic pathway addiction? Nat Rev Cancer 6: 107-116.
10. Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A, Weinberg RA (2008) An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet 40: 499-507.
11. Berdasco M, Esteller M (2010) Aberrant epigenetic landscape in cancer: how cellular identity goes awry. Dev Cell 19: 698-711.
12. Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, Fry B, Meissner A, Wernig M, Plath K, Jaenisch R, Wagschal A, Feil R, Schreiber SL, Lander ES (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125: 315-326.
13. Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16: 6-21.
14. Bird A (2007) Perceptions of epigenetics. Nature 447: 396-398.
15. Blelloch RH, Hochedlinger K, Yamada Y, Brennan C, Kim M, Mintz B, Chin L, Jaenisch R (2004) Nuclear cloning of embryonal carcinoma cells. Proc Natl Acad Sci USA 101: 13985-13990.
16. Bloushtain-Qimron N, Yao J, Snyder EL, Shipitsin M, Campbell LL, Mani SA, Hu M, Chen H, Ustyansky V, Antosiewicz JE, Argani P, Halushka MK, Thomson JA, Pharoah P, Porgador A, Sukumar S, Parsons R, Richardson AL, Stampfer MR, Gelman RS, Nikolskaya T, Nikolsky Y, Polyak K (2008) Cell type-specific DNA methylation patterns in the human breast. Proc Natl Acad Sci USA 105: 14076-14081.
17. Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3: 730-737.
18. Brabletz S, Brabletz T (2010) The ZEB/miR-200 feedback loop-a motor of cellular plasticity in development and cancer? EMBO Rep 11: 670-677.
19. Bracken AP, Helin K (2009) Polycomb group proteins: navigators of lineage pathways led astray in cancer. Nat Rev Cancer 9: 773-784.
20. Bracken AP, Dietrich N, Pasini D, Hansen KH, Helin K (2006) Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions. Genes Dev 20: 1123-1136.
21. Broske AM, Vockentanz L, Kharazi S, Huska MR, Mancini E, Scheller M, Kuhl C, Enns A, Prinz M, Jaenisch R, Nerlov C, Leutz A, Andrade-Navarro MA, Jacobsen SE, Rosenbauer F (2009) DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction. Nat Genet 41: 1207-1215.
22. Campbell LL, Polyak K (2007) Breast tumor heterogeneity: cancer stem cells or clonal evolution? Cell Cycle 6: 2332-2338.
23. Caretti G, Di Padova M, Micales B, Lyons GE, Sartorelli V (2004) The Polycomb Ezh2 methyltransferase regulates muscle gene expression and skeletal muscle differentiation. Genes Dev 18: 2627-2638.
24. Chen X, Hiller M, Sancak Y, Fuller MT (2005) Tissue-specific TAFs counteract Polycomb to turn on terminal differentiation. Science 310: 869-872.
25. Clarkson BD (1974) The survival value of the dormant state in neoplastic and normal cell populations. In: Clarkson B, Baserga R (eds) Control of proliferation in animal cells, vol 1, Cold spring harbor conferences on cell proliferation. Cold Spring Harbor Laboratory, New York, pp 945-972.
26. Cohnheim J (1867) Ueber entzundung und eiterung. Path Anat Physiol Klin Med 40: 1-79.
27. Cox CV, Evely RS, Oakhill A, Pamphilon DH, Goulden NJ, Blair A (2004) Characterization of acute lymphoblastic leukemia progenitor cells. Blood 104: 2919-2925.
28. Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, Shelton AA, Parmiani G, Castelli C, Clarke MF (2007) Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA 104: 10158-10163.
29. Daley GQ (2008) Common themes of dedifferentiation in somatic cell reprogramming and cancer. Cold Spring Harb Symp Quant Biol 73: 171-174.
30. Durante F (1974) Nessofisio-patologico tra la struttura dei nei materni e la genesi di alcuni tumori maligni. Arch Memori ed Osservazioni di Chirurgia Practica 11: 217-2226.
31. Eramo A, Lotti F, Sette G, Pilozzi E, Biffoni M, Di Virgilio A, Conticello C, Ruco L, Peschle C, De Maria R (2008) Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ 15: 504-514.
32. Fang D, Nguyen TK, Leishear K, Finko R, Kulp AN, Hotz S, Van Belle PA, Xu X, Elder DE, Herlyn M (2005) A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res 65: 9328-9337.
33. Feinberg AP, Ohlsson R, Henikoff S (2006) The epigenetic progenitor origin of human cancer. Nat Rev Genet 7(1): 21-33.
34. Ficz G, Branco MR, Seisenberger S, Santos F, Krueger F, Hore TA, Marques CJ, Andrews S, Reik W (2011) Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature 473: 398-402.
35. Garraway LA, Sellers WR (2006) Lineage dependency and lineage-survival oncogenes in human cancer. Nat Rev Cancer 6: 593-602.
36. Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS, Dontu G (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1: 555-567.
37. Goldstein AS, Stoyanova T, Witte ON (2010) Primitive origins of prostate cancer: in vivo evidence for prostate-regenerating cells and prostate cancer-initiating cells. Mol Oncol 4: 385-396.
38. Hawkins RD, Hon GC, Lee LK, Ngo Q, Lister R, Pelizzola M, Edsall LE, Kuan S, Luu Y, Klugman S, Antosiewicz-Bourget J, Ye Z, Espinoza C, Agarwahl S, Shen L, Ruotti V, Wang W, Stewart R, Thomson JA, Ecker JR, Ren B (2010) Distinct epigenomic landscapes of pluripotent and lineage-committed human cells. Cell Stem Cell 6: 479-491.
39. Hemberger M, Dean W, Reik W (2009) Epigenetic dynamics of stem cells and cell lineage commitment: digging Waddington's canal. Nat Rev Mol Cell Biol 10: 526-537.
40. Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ, Heeschen C (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1: 313-323.
41. Hochedlinger K, Blelloch R, Brennan C, Yamada Y, Kim M, Chin L, Jaenisch R (2004) Reprogramming of a melanoma genome by nuclear transplantation. Genes Dev 18: 1875-1885.
42. Howell CY, Bestor TH, Ding F, Latham KE, Mertineit C, Trasler JM, Chaillet JR (2001) Genomic imprinting disrupted by a maternal effect mutation in the Dnmt1 gene. Cell 104: 829-838.
43. Jaenisch R, Bird A (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33(Suppl): 245-254.
44. Jiang F, Qiu Q, Khanna A, Todd NW, Deepak J, Xing L, Wang H, Liu Z, Su Y, Stass SA, Katz RL (2009) Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer. Mol Cancer Res 7: 330-338.
45. Jones PA, Baylin SB (2007) The epigenomics of cancer. Cell 128: 683-692.
46. Kamminga LM, Bystrykh LV, de Boer A, Houwer S, Douma J, Weersing E, Dontje B, de Haan G (2006) The Polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion. Blood 107: 2170-2179.
47. Keshet I, Schlesinger Y, Farkash S, Rand E, Hecht M, Segal E, Pikarski E, Young RA, Niveleau A, Cedar H, Simon I (2006) Evidence for an instructive mechanism of de novo methylation in cancer cells. Nat Genet 38: 149-153.
48. Kim J, Woo AJ, Chu J, Snow JW, Fujiwara Y, Kim CG, Cantor AB, Orkin SH (2010) A Myc network accounts for similarities between embryonic stem and cancer cell transcription programs. Cell 143: 313-324.
49. Koh KP, Yabuuchi A, Rao S, Huang Y, Cunniff K, Nardone J, Laiho A, Tahiliani M, Sommer CA, Mostoslavsky G, Lahesmaa R, Orkin SH, Rodig SJ, Daley GQ, Rao A (2011) Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells. Cell Stem Cell 8: 200-213.
50. Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367: 645-648.
51. Lessard J, Sauvageau G (2003) Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature 423: 255-260.
52. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM (2007) Identification of pancreatic cancer stem cells. Cancer Res 67: 1030-1037.
53. Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR (2009) Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462: 315-322.
54. Lotem J, Sachs L (2006) Epigenetics and the plasticity of differentiation in normal and cancer stem cells. Oncogene 25: 7663-7672.
55. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA (2008) The epithelialmesenchymal transition generates cells with properties of stem cells. Cell 133: 704-715.
56. Marson A, Levine SS, Cole MF, Frampton GM, Brambrink T, Johnstone S, Guenther MG, Johnston WK, Wernig M, Newman J, Calabrese JM, Dennis LM, Volkert TL, Gupta S, Love J, Hannett N, Sharp PA, Bartel DP, Jaenisch R, Young RA (2008) Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells. Cell 134: 521-533.
57. Mayer W, Niveleau A, Walter J, Fundele R, Haaf T (2000) Demethylation of the zygotic paternal genome. Nature 403: 501-502.
58. Meissner A (2010) Epigenetic modifications in pluripotent and differentiated cells. Nat Biotechnol 28: 1079-1088.
59. Meissner A, Mikkelsen TS, Gu H, Wernig M, Hanna J, Sivachenko A, Zhang X, Bernstein BE, Nusbaum C, Jaffe DB, Gnirke A, Jaenisch R, Lander ES (2008) Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature 454: 766-770.
60. Meyer MJ, Fleming JM, Ali MA, Pesesky MW, Ginsburg E, Vonderhaar BK (2009) Dynamic regulation of CD24 and the invasive, CD44posCD24neg phenotype in breast cancer cell lines. Breast Cancer Res 11: R82.
61. Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Kim TK, Koche RP, Lee W, Mendenhall E, O'Donovan A, Presser A, Russ C, Xie X, Meissner A, Wernig M, Jaenisch R, Nusbaum C, Lander ES, Bernstein BE (2007) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448: 553-560.
62. Milne TA, Martin ME, Brock HW, Slany RK, Hess JL (2005) Leukemogenic MLL fusion proteins bind across a broad region of the Hox a9 locus, promoting transcription and multiple histone modifications. Cancer Res 65: 11367-11374.
63. Molofsky AV, Pardal R, Iwashita T, Park IK, Clarke MF, Morrison SJ (2003) Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 425: 962-967.
64. Morgan HD, Santos F, Green K, Dean W, Reik W (2005) Epigenetic reprogramming in mammals. Hum Mol Genet 14(Spec No 1): R47-R58.
65. Myant K, Termanis A, Sundaram AY, Boe T, Li C, Merusi C, Burrage J, de Las Heras JI, Stancheva I (2011) LSH and G9a/GLP complex are required for developmentally programmed DNA methylation. Genome Res 21: 83-94.
66. Nowell PC (1976) The clonal evolution of tumor cell populations. Science 194: 23-28.
67. O'Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445: 106-110.
68. Ohm JE, McGarvey KM, Yu X, Cheng L, Schuebel KE, Cope L, Mohammad HP, Chen W, Daniel VC, Yu W, Berman DM, Jenuwein T, Pruitt K, Sharkis SJ, Watkins DN, Herman JG, Baylin SB (2007) A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing. Nat Genet 39: 237-242.
69. Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99: 247-257.
70. Oswald J, Engemann S, Lane N, Mayer W, Olek A, Fundele R, Dean W, Reik W, Walter J (2000) Active demethylation of the paternal genome in the mouse zygote. Curr Biol 10: 475-478.
71. Pastor WA, Pape UJ, Huang Y, Henderson HR, Lister R, Ko M, McLoughlin EM, Brudno Y, Mahapatra S, Kapranov P, Tahiliani M, Daley GQ, Liu XS, Ecker JR, Milos PM, Agarwal S, Rao A (2011) Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells. Nature 473: 394-397.
72. Pauli A, Rinn JL, Schier AF (2011) Non-coding RNAs as regulators of embryogenesis. Nat Rev Genet 12: 136-149.
73. Pierce GB, Johnson LD (1971) Differentiation and cancer. In Vitro 7: 140-145.
74. Pietersen AM, Evers B, Prasad AA, Tanger E, Cornelissen-Steijger P, Jonkers J, van Lohuizen M (2008) Bmi1 regulates stem cells and proliferation and differentiation of committed cells in mammary epithelium. Curr Biol 18: 1094-1099.
75. Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, Weissman IL, Clarke MF, Ailles LE (2007) Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA 104: 973-978.
76. Rajasekhar VK, Studer L, Gerald W, Socci ND, Scher HI (2011) Tumour-initiating stem-like cells in human prostate cancer exhibit increased NF-kappaB signalling. Nat Commun 2: 162.
77. Ran D, Schubert M, Pietsch L, Taubert I, Wuchter P, Eckstein V, Bruckner T, Zoeller M, Ho AD (2009) Aldehyde dehydrogenase activity among primary leukemia cells is associated with stem cell features and correlates with adverse clinical outcomes. Exp Hematol 37: 1423-1434.
78. Roesch A, Fukunaga-Kalabis M, Schmidt EC, Zabierowski SE, Brafford PA, Vultur A, Basu D, Gimotty P, Vogt T, Herlyn M (2010) A temporarily distinct subpopulation of slow-cycling melanoma cells is required for continuous tumor growth. Cell 141: 583-594.
79. Sangiorgi E, Capecchi MR (2008) Bmi1 is expressed in vivo in intestinal stem cells. Nat Genet 40: 915-920.
80. Santos F, Hendrich B, Reik W, Dean W (2002) Dynamic reprogramming of DNA methylation in the early mouse embryo. Dev Biol 241: 172-182.
81. Sasaki H, Matsui Y (2008) Epigenetic events in mammalian germ-cell development: reprogramming and beyond. Nat Rev Genet 9: 129-140.
82. Schatton T, Murphy GF, Frank NY, Yamaura K, Waaga-Gasser AM, Gasser M, Zhan Q, Jordan S, Duncan LM, Weishaupt C, Fuhlbrigge RC, Kupper TS, Sayegh MH, Frank MH (2008) Identification of cells initiating human melanomas. Nature 451: 345-349.
83. Schlesinger Y, Straussman R, Keshet I, Farkash S, Hecht M, Zimmerman J, Eden E, Yakhini Z, Ben-Shushan E, Reubinoff BE, Bergman Y, Simon I, Cedar H (2007) Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nat Genet 39: 232-236.
84. Sell S, Pierce GB (1994) Maturation arrest of stem cell differentiation is a common pathway for the cellular origin of teratocarcinomas and epithelial cancers. Lab Invest 70: 6-22.
85. Sen GL (2011) Remembering one's identity: the epigenetic basis of stem cell fate decisions. FASEB J 25(7): 2123-2128.
86. Sen GL, Reuter JA, Webster DE, Zhu L, Khavari PA (2010) DNMT1 maintains progenitor function in self-renewing somatic tissue. Nature 463: 563-567.
87. Sharma S, Kelly TK, Jones PA (2010) Epigenetics in cancer. Carcinogenesis 31: 27-36.
88. Shen Y, Chow J, Wang Z, Fan G (2006) Abnormal CpG island methylation occurs during in vitro differentiation of human embryonic stem cells. Hum Mol Genet 15: 2623-2635.
89. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63: 5821-5828.
90. Sperger JM, Chen X, Draper JS, Antosiewicz JE, Chon CH, Jones SB, Brooks JD, Andrews PW, Brown PO, Thomson JA (2003) Gene expression patterns in human embryonic stem cells and human pluripotent germ cell tumors. Proc Natl Acad Sci USA 100: 13350-13355.
91. Sun C, Liu YK (2011) Induced pluripotent cancer cells: progress and application. J Cancer Res Clin Oncol 137: 1-8.
92. Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324: 930-935.
93. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adultfibroblast cultures by defined factors. Cell 126: 663-676.
94. Takaishi S, Okumura T, Tu S, Wang SS, Shibata W, Vigneshwaran R, Gordon SA, Shimada Y, Wang TC (2009) Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells 27: 1006-1020.
95. Tang DG, Patrawala L, Calhoun T, Bhatia B, Choy G, Schneider-Broussard R, Jeter C (2007) Prostate cancer stem/progenitor cells: identification, characterization, and implications. Mol Carcinog 46: 1-14.
96. Tay Y, Zhang J, Thomson AM, Lim B, Rigoutsos I (2008) MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature 455: 1124-1128.
97. Telerman A, Amson R (2009) The molecular programme of tumour reversion: the steps beyond malignant transformation. Nat Rev Cancer 9: 206-216.
98. Thiery JP, Acloque H, Huang RY, Nieto MA (2009) Epithelial-mesenchymal transitions in development and disease. Cell 139(5): 871-890.
99. Tirino V, Desiderio V, d'Aquino R, De Francesco F, Pirozzi G, Graziano A, Galderisi U, Cavaliere C, De Rosa A, Papaccio G, Giordano A (2008) Detection and characterization of CD133+ cancer stem cells in human solid tumours. PLoS One 3: e3469.
100. Trowbridge JJ, Snow JW, Kim J, Orkin SH (2009) DNA methyltransferase 1 is essential for and uniquely regulates hematopoietic stem and progenitor cells. Cell Stem Cell 5: 442-449.
101. Turner BM (2007) Defining an epigenetic code. Nat Cell Biol 9: 2-6.
102. Virchow R (1855) Editorial Archiv fuer pathologische Anatomie und Physiologie und fuer klinisque Madizin 8: 23-54.
103. Vire E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C, Morey L, Van Eynde A, Bernard D, Vanderwinden JM, Bollen M, Esteller M, Di Croce L, de Launoit Y, Fuks F (2006) The Polycomb group protein EZH2 directly controls DNA methylation. Nature 439: 871-874.
104. Visvader JE (2011) Cells of origin in cancer. Nature 469: 314-322.
105. Visvader JE, Lindeman GJ (2008) Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer 8: 755-768.
106. Waddington CH (1935) Cancer and the theory of organisers. Nature 135: 606-608.
107. Waddington CH (1940) Organisers & genes. Cambridge University Press, Cambridge, UK.
108. Wang JCY, Dick JE (2005) Cancer stem cells: lessons from leukemia. Trends Cell Biol 15: 494-501.
109. Widschwendter M, Fiegl H, Egle D, Mueller-Holzner E, Spizzo G, Marth C, Weisenberger DJ, Campan M, Young J, Jacobs I, Laird PW (2007) Epigenetic stem cell signature in cancer. Nat Genet 39: 157-158.
110. Wossidlo M, Arand J, Sebastiano V, Lepikhov K, Boiani M, Reinhardt R, Scholer H, Walter J (2010) Dynamic link of DNA demethylation, DNA strand breaks and repair in mouse zygotes. EMBO J 29: 1877-1888.
111. Wossidlo M, Nakamura T, Lepikhov K, Marques CJ, Zakhartchenko V, Boiani M, Arand J, Nakano T, Reik W, Walter J (2011) 5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming. Nat Commun 2: 241.
112. Wray J, Kalkan T, Smith AG (2010) The ground state of pluripotency. Biochem Soc Trans 38: 1027-1032.
113. Xu N, Papagiannakopoulos T, Pan G, Thomson JA, Kosik KS (2009) MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell 137: 647-658.
114. Xu Y, Wu F, Tan L, Kong L, Xiong L, Deng J, Barbera AJ, Zheng L, Zhang H, Huang S, Min J, Nicholson T, Chen T, Xu G, Shi Y, Zhang K, Shi YG (2011) Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells. Mol Cell 42: 451-464.
115. Yang ZF, Ho DW, Ng MN, Lau CK, Yu WC, Ngai P, Chu PW, Lam CT, Poon RT, Fan ST (2008) Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell 13: 153-166.
116. Young RA (2011) Control of the embryonic stem cell state. Cell 144: 940-954.
117. Zhang S, Balch C, Chan MW, Lai HC, Matei D, Schilder JM, Yan PS, Huang TH, Nephew KP (2008) Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res 68: 4311-4320.
118. Zimmerman AL, Wu S (2011) MicroRNAs, cancer and cancer stem cells. Cancer Lett 300: 10-19.