Cellular Reprogramming Technology for Dissecting Cancer Epigenome in Vivo

References

• Feinberg AP , VogelsteinB . Hypomethylation distinguishes genes of some human cancers from their normal counterparts . Nature301 ( 5895 ), 89 – 92 ( 1983 ).
   PubMed Web of Science ®Google Scholar
• Riggs AD , JonesPA . 5-methylcytosine, gene regulation, and cancer . Adv. Cancer Res.40 , 1 – 30 ( 1983 ).
   PubMed Web of Science ®Google Scholar
• Jones PA , BaylinSB . The epigenomics of cancer . Cell128 ( 4 ), 683 – 692 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Belinsky SA , NikulaKJ , PalmisanoWAet al. Aberrant methylation of p16(INK4a) is an early event in lung cancer and a potential biomarker for early diagnosis . Proc. Natl Acad. Sci. USA95 ( 20 ), 11891 – 11896 ( 1998 ).
   PubMed Web of Science ®Google Scholar
• Herman JG , LatifF , WengYet al. Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma . Proc. Natl Acad. Sci. USA91 ( 21 ), 9700 – 9704 ( 1994 ).
   PubMed Web of Science ®Google Scholar
• Esteller M , SilvaJM , DominguezGet al. Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors . J. Natl Cancer Inst.92 ( 7 ), 564 – 569 ( 2000 ).
   PubMedGoogle Scholar
• Laird PW , Jackson-GrusbyL , FazeliAet al. Suppression of intestinal neoplasia by DNA hypomethylation . Cell81 ( 2 ), 197 – 205 ( 1995 ).
   PubMed Web of Science ®Google Scholar
• Chen RZ , PetterssonU , BeardC , Jackson-GrusbyL , JaenischR . DNA hypomethylation leads to elevated mutation rates . Nature395 ( 6697 ), 89 – 93 ( 1998 ).
   PubMed Web of Science ®Google Scholar
• Eden A , GaudetF , WaghmareA , JaenischR . Chromosomal instability and tumors promoted by DNA hypomethylation . Science300 ( 5618 ), 455 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Gaudet F , HodgsonJG , EdenAet al. Induction of tumors in mice by genomic hypomethylation . Science300 ( 5618 ), 489 – 492 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Yamada Y , Jackson-GrusbyL , LinhartHet al. Opposing effects of DNA hypomethylation on intestinal and liver carcinogenesis . Proc. Natl Acad. Sci. USA102 ( 38 ), 13580 – 13585 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Lin H , YamadaY , NguyenSet al. Suppression of intestinal neoplasia by deletion of Dnmt3b . Mol. Cell. Biol.26 ( 8 ), 2976 – 2983 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Linhart HG , LinH , YamadaYet al. Dnmt3b promotes tumorigenesis in vivo by gene-specific de novo methylation and transcriptional silencing . Genes Dev.21 ( 23 ), 3110 – 3122 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Hatano Y , SemiK , HashimotoKet al. Reducing DNA methylation suppresses colon carcinogenesis by inducing tumor cell differentiation . Carcinogenesis36 ( 7 ), 719 – 729 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Challen GA , SunD , JeongMet al. Dnmt3a is essential for hematopoietic stem cell differentiation . Nat. Genet.44 ( 1 ), 23 – 31 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Zhang X , SuJ , JeongMet al. DNMT3A and TET2 compete and cooperate to repress lineage-specific transcription factors in hematopoietic stem cells . Nat. Genet.48 ( 9 ), 1014 – 1023 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Reik W , SuraniMA . Germline and pluripotent stem cells . Cold Spring Harb. Perspect. Biol.7 ( 11 ), pii:a019422 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Reik W , WalterJ . Genomic imprinting: parental influence on the genome . Nat. Rev. Genet.2 ( 1 ), 21 – 32 ( 2001 ).
   PubMed Web of Science ®Google Scholar
• Ogawa O , EcclesMR , SzetoJet al. Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms’ tumour . Nature362 ( 6422 ), 749 – 751 ( 1993 ).
   PubMed Web of Science ®Google Scholar
• Steenman MJ , RainierS , DobryCJ , GrundyP , HoronIL , FeinbergAP . Loss of imprinting of IGF2 is linked to reduced expression and abnormal methylation of H19 in Wilms’ tumour . Nat. Genet.7 ( 3 ), 433 – 439 ( 1994 ).
   PubMed Web of Science ®Google Scholar
• Holm TM , Jackson-GrusbyL , BrambrinkT , YamadaY , RideoutWM3rd , JaenischR . Global loss of imprinting leads to widespread tumorigenesis in adult mice . Cancer Cell8 ( 4 ), 275 – 285 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Ng JM , MartinezD , MarshEDet al. Generation of a mouse model of atypical teratoid/rhabdoid tumor of the central nervous system through combined deletion of Snf5 and p53 . Cancer Res.75 ( 21 ), 4629 – 4639 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Richly H , AloiaL , Di CroceL . Roles of the Polycomb group proteins in stem cells and cancer . Cell Death Dis.2 , e204 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Portela A , EstellerM . Epigenetic modifications and human disease . Nat. Biotechnol.28 ( 10 ), 1057 – 1068 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Mochizuki-Kashio M , AoyamaK , SashidaGet al. Ezh2 loss in hematopoietic stem cells predisposes mice to develop heterogeneous malignancies in an Ezh1-dependent manner . Blood126 ( 10 ), 1172 – 1183 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Lund K , AdamsPD , CoplandM . EZH2 in normal and malignant hematopoiesis . Leukemia28 ( 1 ), 44 – 49 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Plass C , PfisterSM , LindrothAM , BogatyrovaO , ClausR , LichterP . Mutations in regulators of the epigenome and their connections to global chromatin patterns in cancer . Nat. Rev. Genet.14 ( 11 ), 765 – 780 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Lawrence MS , StojanovP , MermelCHet al. Discovery and saturation analysis of cancer genes across 21 tumour types . Nature505 ( 7484 ), 495 – 501 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Feinberg AP , KoldobskiyMA , GondorA . Epigenetic modulators, modifiers and mediators in cancer aetiology and progression . Nat. Rev. Genet.17 ( 5 ), 284 – 299 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Delhommeau F , DupontS , Della ValleVet al. Mutation in TET2 in myeloid cancers . N. Engl. J. Med.360 ( 22 ), 2289 – 2301 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Ley TJ , DingL , WalterMJet al. DNMT3A mutations in acute myeloid leukemia . N. Engl. J. Med.363 ( 25 ), 2424 – 2433 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Kim KH , RobertsCW . Targeting EZH2 in cancer . Nat. Med.22 ( 2 ), 128 – 134 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Wu G , BroniscerA , MceachronTAet al. Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas . Nat. Genet.44 ( 3 ), 251 – 253 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Schwartzentruber J , KorshunovA , LiuXYet al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma . Nature482 ( 7384 ), 226 – 231 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Jones S , WangTL , Shih IeMet al. Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma . Science330 ( 6001 ), 228 – 231 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Shibata T , AburataniH . Exploration of liver cancer genomes . Nat. Rev. Gastroenterol. Hepatol.11 ( 6 ), 340 – 349 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Watson IR , TakahashiK , FutrealPA , ChinL . Emerging patterns of somatic mutations in cancer . Nat. Rev. Genet.14 ( 10 ), 703 – 718 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Zaret KS , CarrollJS . Pioneer transcription factors: establishing competence for gene expression . Genes Dev.25 ( 21 ), 2227 – 2241 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Zaret KS , MangoSE . Pioneer transcription factors, chromatin dynamics, and cell fate control . Curr. Opin. Genet. Dev.37 , 76 – 81 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Perino M , VeenstraGJ . Chromatin control of developmental dynamics and plasticity . Dev. Cell38 ( 6 ), 610 – 620 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• De La Rica L , Rodriguez-UbrevaJ , GarciaMet al. PU.1 target genes undergo Tet2-coupled demethylation and DNMT3b-mediated methylation in monocyte-to-osteoclast differentiation . Genome Biol.14 ( 9 ), R99 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Ficz G , HoreTA , SantosFet al. FGF signaling inhibition in ESCs drives rapid genome-wide demethylation to the epigenetic ground state of pluripotency . Cell Stem Cell13 ( 3 ), 351 – 359 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Habibi E , BrinkmanAB , ArandJet al. Whole-genome bisulfite sequencing of two distinct interconvertible DNA methylomes of mouse embryonic stem cells . Cell Stem Cell13 ( 3 ), 360 – 369 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Downward J . Targeting RAS signalling pathways in cancer therapy . Nat. Rev. Cancer3 ( 1 ), 11 – 22 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Agger K , CloosPA , RudkjaerLet al. The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene- and stress-induced senescence . Genes Dev.23 ( 10 ), 1171 – 1176 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Riquelme E , BehrensC , LinHYet al. Modulation of EZH2 expression by MEK-ERK or PI3K-AKT signaling in lung cancer is dictated by different KRAS oncogene mutations . Cancer Res.76 ( 3 ), 675 – 685 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Balkwill F , MantovaniA . Inflammation and cancer: back to Virchow?Lancet357 ( 9255 ), 539 – 545 ( 2001 ).
   PubMed Web of Science ®Google Scholar
• Mima K , NishiharaR , QianZRet al. Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis . Gut65 ( 12 ), 1973 – 1980 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Tahara T , YamamotoE , SuzukiHet al. Fusobacterium in colonic flora and molecular features of colorectal carcinoma . Cancer Res.74 ( 5 ), 1311 – 1318 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Reuter S , GuptaSC , ChaturvediMM , AggarwalBB . Oxidative stress, inflammation, and cancer: how are they linked?Free Radic. Biol. Med.49 ( 11 ), 1603 – 1616 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Niwa T , TsukamotoT , ToyodaTet al. Inflammatory processes triggered by Helicobacter pylori infection cause aberrant DNA methylation in gastric epithelial cells . Cancer Res.70 ( 4 ), 1430 – 1440 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Okamoto Y , ShinjoK , ShimizuYet al. Hepatitis virus infection affects DNA methylation in mice with humanized livers . Gastroenterology146 ( 2 ), 562 – 572 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Hattori N , UshijimaT . Epigenetic impact of infection on carcinogenesis: mechanisms and applications . Genome Med.8 ( 1 ), 10 ( 2016 ).
   PubMedGoogle Scholar
• Ushijima T . Epigenetic field for cancerization . J. Biochem. Mol. Biol.40 ( 2 ), 142 – 150 ( 2007 ).
   PubMedGoogle Scholar
• Shimazu T , AsadaK , CharvatHet al. Association of gastric cancer risk factors with DNA methylation levels in gastric mucosa of healthy Japanese: a cross-sectional study . Carcinogenesis36 ( 11 ), 1291 – 1298 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Chiba T , MarusawaH , UshijimaT . Inflammation-associated cancer development in digestive organs: mechanisms and roles for genetic and epigenetic modulation . Gastroenterology143 ( 3 ), 550 – 563 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Ogino S , LochheadP , ChanATet al. Molecular pathological epidemiology of epigenetics: emerging integrative science to analyze environment, host, and disease . Mod. Pathol.26 ( 4 ), 465 – 484 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Rescigno T , MicolucciL , TecceMF , CapassoA . Bioactive nutrients and nutrigenomics in age-related diseases . Molecules22 ( 1 ), ( 2017 ).
   PubMed Web of Science ®Google Scholar
• Barrow TM , MichelsKB . Epigenetic epidemiology of cancer . Biochem. Biophys. Res. Commun.455 ( 1–2 ), 70 – 83 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Ng JM , YuJ . Promoter hypermethylation of tumour suppressor genes as potential biomarkers in colorectal cancer . Int. J. Mol. Sci.16 ( 2 ), 2472 – 2496 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Toyota M , AhujaN , Ohe-ToyotaM , HermanJG , BaylinSB , IssaJP . CpG island methylator phenotype in colorectal cancer . Proc. Natl Acad. Sci. USA96 ( 15 ), 8681 – 8686 ( 1999 ).
   PubMed Web of Science ®Google Scholar
• Suzuki H , YamamotoE , MaruyamaR , NiinumaT , KaiM . Biological significance of the CpG island methylator phenotype . Biochem. Biophys. Res. Commun.455 ( 1–2 ), 35 – 42 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Nishihara R , MorikawaT , KuchibaAet al. A prospective study of duration of smoking cessation and colorectal cancer risk by epigenetics-related tumor classification . Am. J. Epidemiol.178 ( 1 ), 84 – 100 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Samowitz WS , AlbertsenH , SweeneyCet al. Association of smoking, CpG island methylator phenotype, and V600E BRAF mutations in colon cancer . J. Natl Cancer Inst.98 ( 23 ), 1731 – 1738 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Russo AL , ThiagalingamA , PanHet al. Differential DNA hypermethylation of critical genes mediates the stage-specific tobacco smoke-induced neoplastic progression of lung cancer . Clin. Cancer Res.11 ( 7 ), 2466 – 2470 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Shinjo K , OkamotoY , AnBet al. Integrated analysis of genetic and epigenetic alterations reveals CpG island methylator phenotype associated with distinct clinical characters of lung adenocarcinoma . Carcinogenesis33 ( 7 ), 1277 – 1285 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Vaissiere T , HungRJ , ZaridzeDet al. Quantitative analysis of DNA methylation profiles in lung cancer identifies aberrant DNA methylation of specific genes and its association with gender and cancer risk factors . Cancer Res.69 ( 1 ), 243 – 252 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Curtin K , SlatteryML , SamowitzWS . CpG island methylation in colorectal cancer: past, present and future . Patholog. Res. Int. 2011 , 902674 ( 2011 ).
   PubMedGoogle Scholar
• Nakazawa MS , KeithB , SimonMC . Oxygen availability and metabolic adaptations . Nat. Rev. Cancer16 ( 10 ), 663 – 673 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Thienpont B , SteinbacherJ , ZhaoHet al. Tumour hypoxia causes DNA hypermethylation by reducing TET activity . Nature537 ( 7618 ), 63 – 68 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Reik W . Stability and flexibility of epigenetic gene regulation in mammalian development . Nature447 ( 7143 ), 425 – 432 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Long HK , PrescottSL , WysockaJ . Ever-changing landscapes: transcriptional enhancers in development and evolution . Cell167 ( 5 ), 1170 – 1187 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Iwafuchi-Doi M , ZaretKS . Cell fate control by pioneer transcription factors . Development143 ( 11 ), 1833 – 1837 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Soufi A , GarciaMF , JaroszewiczA , OsmanN , PellegriniM , ZaretKS . Pioneer transcription factors target partial DNA motifs on nucleosomes to initiate reprogramming . Cell161 ( 3 ), 555 – 568 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Smith ZD , MeissnerA . DNA methylation: roles in mammalian development . Nat. Rev. Genet.14 ( 3 ), 204 – 220 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Chen T , DentSY . Chromatin modifiers and remodellers: regulators of cellular differentiation . Nat. Rev. Genet.15 ( 2 ), 93 – 106 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Boyer LA , PlathK , ZeitlingerJet al. Polycomb complexes repress developmental regulators in murine embryonic stem cells . Nature441 ( 7091 ), 349 – 353 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Lee TI , JennerRG , BoyerLAet al. Control of developmental regulators by Polycomb in human embryonic stem cells . Cell125 ( 2 ), 301 – 313 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Harikumar A , MeshorerE . Chromatin remodeling and bivalent histone modifications in embryonic stem cells . EMBO Rep.16 ( 12 ), 1609 – 1619 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Geisler SJ , ParoR . Trithorax and Polycomb group-dependent regulation: a tale of opposing activities . Development142 ( 17 ), 2876 – 2887 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Schuettengruber B , CavalliG . Recruitment of polycomb group complexes and their role in the dynamic regulation of cell fate choice . Development136 ( 21 ), 3531 – 3542 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Schuettengruber B , MartinezAM , IovinoN , CavalliG . Trithorax group proteins: switching genes on and keeping them active . Nat. Rev. Mol. Cell Biol.12 ( 12 ), 799 – 814 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Voigt P , TeeWW , ReinbergD . A double take on bivalent promoters . Genes Dev.27 ( 12 ), 1318 – 1338 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Holmberg J , PerlmannT . Maintaining differentiated cellular identity . Nat. Rev. Genet.13 ( 6 ), 429 – 439 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Jaenisch R , BirdA . Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals . Nat. Genet.33 ( Suppl. ), 245 – 254 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Wu SC , ZhangY . Active DNA demethylation: many roads lead to Rome . Nat. Rev. Mol. Cell Biol.11 ( 9 ), 607 – 620 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Barker N , RidgwayRA , Van EsJHet al. Crypt stem cells as the cells-of-origin of intestinal cancer . Nature457 ( 7229 ), 608 – 611 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Bonnet D , DickJE . Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell . Nat. Med.3 ( 7 ), 730 – 737 ( 1997 ).
   PubMed Web of Science ®Google Scholar
• Schwitalla S , FingerleAA , CammareriPet al. Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties . Cell152 ( 1–2 ), 25 – 38 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Friedmann-Morvinski D , BushongEA , KeEet al. Dedifferentiation of neurons and astrocytes by oncogenes can induce gliomas in mice . Science338 ( 6110 ), 1080 – 1084 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Gurdon JB . The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles . J. Embryol. Exp. Morphol.10 , 622 – 640 ( 1962 ).
   PubMedGoogle Scholar
• Campbell KH , McwhirJ , RitchieWA , WilmutI . Sheep cloned by nuclear transfer from a cultured cell line . Nature380 ( 6569 ), 64 – 66 ( 1996 ).
   PubMed Web of Science ®Google Scholar
• Wakayama T , PerryAC , ZuccottiM , JohnsonKR , YanagimachiR . Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei . Nature394 ( 6691 ), 369 – 374 ( 1998 ).
   PubMed Web of Science ®Google Scholar
• Tachibana M , AmatoP , SparmanMet al. Human embryonic stem cells derived by somatic cell nuclear transfer . Cell153 ( 6 ), 1228 – 1238 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Matoba S , LiuY , LuFet al. Embryonic development following somatic cell nuclear transfer impeded by persisting histone methylation . Cell159 ( 4 ), 884 – 895 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Rodriguez-Osorio N , UrregoR , CibelliJB , EilertsenK , MemiliE . Reprogramming mammalian somatic cells . Theriogenology78 ( 9 ), 1869 – 1886 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Jullien J , VodnalaM , PasqueVet al. Gene resistance to transcriptional reprogramming following nuclear transfer is directly mediated by multiple chromatin-repressive pathways . Mol. Cell65 ( 5 ), 873 – 884 , e878 ( 2017 ).
   PubMed Web of Science ®Google Scholar
• Takahashi K , YamanakaS . Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors . Cell126 ( 4 ), 663 – 676 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Takahashi K , TanabeK , OhnukiMet al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors . Cell131 ( 5 ), 861 – 872 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Gidekel S , PizovG , BergmanY , PikarskyE . Oct-3/4 is a dose-dependent oncogenic fate determinant . Cancer Cell4 ( 5 ), 361 – 370 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Hochedlinger K , YamadaY , BeardC , JaenischR . Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues . Cell121 ( 3 ), 465 – 477 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Boumahdi S , DriessensG , LapougeGet al. SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell carcinoma . Nature511 ( 7508 ), 246 – 250 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Ben-Porath I , ThomsonMW , CareyVJet al. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors . Nat. Genet.40 ( 5 ), 499 – 507 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Hong H , TakahashiK , IchisakaTet al. Suppression of induced pluripotent stem cell generation by the p53-p21 pathway . Nature460 ( 7259 ), 1132 – 1135 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Utikal J , PoloJM , StadtfeldMet al. Immortalization eliminates a roadblock during cellular reprogramming into iPS cells . Nature460 ( 7259 ), 1145 – 1148 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• De Craene B , BerxG . Regulatory networks defining EMT during cancer initiation and progression . Nat. Rev. Cancer13 ( 2 ), 97 – 110 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Davis RL , WeintraubH , LassarAB . Expression of a single transfected cDNA converts fibroblasts to myoblasts . Cell51 ( 6 ), 987 – 1000 ( 1987 ).
   PubMed Web of Science ®Google Scholar
• Xie H , YeM , FengR , GrafT . Stepwise reprogramming of B cells into macrophages . Cell117 ( 5 ), 663 – 676 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Ieda M , FuJD , Delgado-OlguinPet al. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors . Cell142 ( 3 ), 375 – 386 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Vierbuchen T , OstermeierA , PangZP , KokubuY , SudhofTC , WernigM . Direct conversion of fibroblasts to functional neurons by defined factors . Nature463 ( 7284 ), 1035 – 1041 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Zhou Q , BrownJ , KanarekA , RajagopalJ , MeltonDA . In vivo reprogramming of adult pancreatic exocrine cells to beta-cells . Nature455 ( 7213 ), 627 – 632 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Zhang J , ChenS , ZhangDet al. Tet3-mediated DNA demethylation contributes to the direct conversion of fibroblast to functional neuron . Cell Rep.17 ( 9 ), 2326 – 2339 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Smith DK , YangJ , LiuML , ZhangCL . Small molecules modulate chromatin accessibility to promote NEUROG2-mediated fibroblast-to-neuron reprogramming . Stem Cell Rep.7 ( 5 ), 955 – 969 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Liu Z , ChenO , ZhengMet al. Re-patterning of H3K27me3, H3K4me3 and DNA methylation during fibroblast conversion into induced cardiomyocytes . Stem Cell Res.16 ( 2 ), 507 – 518 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Blelloch RH , HochedlingerK , YamadaYet al. Nuclear cloning of embryonal carcinoma cells . Proc. Natl Acad. Sci. USA101 ( 39 ), 13985 – 13990 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Hochedlinger K , BlellochR , BrennanCet al. Reprogramming of a melanoma genome by nuclear transplantation . Genes Dev.18 ( 15 ), 1875 – 1885 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Stadtfeld M , MaheraliN , BorkentM , HochedlingerK . A reprogrammable mouse strain from gene-targeted embryonic stem cells . Nat. Methods7 ( 1 ), 53 – 55 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Ohnishi K , SemiK , YamamotoTet al. Premature termination of reprogramming in vivo leads to cancer development through altered epigenetic regulation . Cell156 ( 4 ), 663 – 677 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Abad M , MosteiroL , PantojaCet al. Reprogramming in vivo produces teratomas and iPS cells with totipotency features . Nature502 ( 7471 ), 340 – 345 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Little MH , DunnR , ByrneJAet al. Equivalent expression of paternally and maternally inherited WT1 alleles in normal fetal tissue and Wilms’ tumours . Oncogene7 ( 4 ), 635 – 641 ( 1992 ).
   PubMed Web of Science ®Google Scholar
• Major MB , CampND , BerndtJDet al. Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling . Science316 ( 5827 ), 1043 – 1046 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Aiden AP , RiveraMN , RheinbayEet al. Wilms tumor chromatin profiles highlight stem cell properties and a renal developmental network . Cell Stem Cell6 ( 6 ), 591 – 602 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Apostolou E , HochedlingerK . Chromatin dynamics during cellular reprogramming . Nature502 ( 7472 ), 462 – 471 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Semi K , YamadaY . Induced pluripotent stem cell technology for dissecting the cancer epigenome . Cancer Sci.106 ( 10 ), 1251 – 1256 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Ohnishi K , SemiK , YamadaY . Epigenetic regulation leading to induced pluripotency drives cancer development in vivo . Biochem. Biophys. Res. Commun.455 ( 1–2 ), 10 – 15 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Yamada Y , HagaH , YamadaY . Concise review: dedifferentiation meets cancer development: proof of concept for epigenetic cancer . Stem Cells Transl. Med.3 ( 10 ), 1182 – 1187 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Buganim Y , FaddahDA , ChengAWet al. Single-cell expression analyses during cellular reprogramming reveal an early stochastic and a late hierarchic phase . Cell150 ( 6 ), 1209 – 1222 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Buganim Y , MarkoulakiS , Van WietmarschenNet al. The developmental potential of iPSCs is greatly influenced by reprogramming factor selection . Cell Stem Cell15 ( 3 ), 295 – 309 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Liu Y , ChengH , GaoSet al. Reprogramming of MLL-AF9 leukemia cells into pluripotent stem cells . Leukemia28 ( 5 ), 1071 – 1080 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Kim J , HoffmanJP , AlpaughRKet al. An iPSC line from human pancreatic ductal adenocarcinoma undergoes early to invasive stages of pancreatic cancer progression . Cell Rep.3 ( 6 ), 2088 – 2099 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Stricker SH , FeberA , EngstromPGet al. Widespread resetting of DNA methylation in glioblastoma-initiating cells suppresses malignant cellular behavior in a lineage-dependent manner . Genes Dev.27 ( 6 ), 654 – 669 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Hashimoto K , YamadaY , SemiKet al. Cellular context-dependent consequences of Apc mutations on gene regulation and cellular behavior . Proc. Natl Acad. Sci. USA114 ( 4 ), 758 – 763 ( 2017 ).
   PubMed Web of Science ®Google Scholar
• Liu XS , WuH , JiXet al. Editing DNA methylation in the mammalian genome . Cell167 ( 1 ), 233.e217 – 247.e217 ( 2016 ).
   Web of Science ®Google Scholar
• Morita S , NoguchiH , HoriiTet al. Targeted DNA demethylation in vivo using dCas9-peptide repeat and scFv-TET1 catalytic domain fusions . Nat. Biotechnol.34 ( 10 ), 1060 – 1065 ( 2016 ).
   PubMed Web of Science ®Google Scholar