Transcriptional Control of Somatic Cell Reprogramming.

Somatic cells and pluripotent cells display remarkable differences in most aspects of cell function. Accordingly, somatic cell reprogramming by exogenous factors requires comprehensive changes in gene transcription to induce a forced pluripotent state, which is encompassed by a simultaneous transformation of the epigenome. Nevertheless, how the reprogramming factors and other endogenous regulators coordinate to suppress the somatic cell gene program and activate the pluripotency gene network, and why the conversion is multi-phased and lengthy, remain enigmatic. We summarize the current knowledge of transcriptional regulation in somatic cell reprogramming, and highlight new perspectives that may help to reshape existing paradigms.

[1]  Mo Li,et al.  Navigating the epigenetic landscape of pluripotent stem cells , 2012, Nature Reviews Molecular Cell Biology.

[2]  Robert Lanza,et al.  Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. , 2009, Cell stem cell.

[3]  Jason D. Buenrostro,et al.  Transient Acquisition of Pluripotency During Somatic Cell Transdifferentiation with iPSC Reprogramming Factors , 2015, Nature Biotechnology.

[4]  A. Link,et al.  Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA. , 2003, Molecular cell.

[5]  K. Zhao,et al.  Extended Self-Renewal and Accelerated Reprogramming in the Absence of Kdm5b , 2013, Molecular and Cellular Biology.

[6]  K. Baumann.  Epigenetics: Enhancers under TET control , 2014, Nature Reviews Molecular Cell Biology.

[7]  Rong Fan,et al.  Nonstochastic Reprogramming from a Privileged Somatic Cell State , 2014, Cell.

[8]  Bing Lim,et al.  A precarious balance: pluripotency factors as lineage specifiers. , 2011, Cell stem cell.

[9]  J. Wrana,et al.  A late transition in somatic cell reprogramming requires regulators distinct from the pluripotency network. , 2012, Cell stem cell.

[10]  H. Schöler,et al.  Generation of Human‐Induced Pluripotent Stem Cells in the Absence of Exogenous Sox2 , 2009, Stem cells.

[11]  Stuart H. Orkin,et al.  A Myc Network Accounts for Similarities between Embryonic Stem and Cancer Cell Transcription Programs , 2010, Cell.

[12]  J. Rinn,et al.  Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells , 2010, Nature Genetics.

[13]  D. Pei,et al.  Srebp‐1 Interacts with c‐Myc to Enhance Somatic Cell Reprogramming , 2016, Stem cells.

[14]  Marius Wernig,et al.  c-Myc is dispensable for direct reprogramming of mouse fibroblasts. , 2008, Cell stem cell.

[15]  H. Schöler,et al.  A combined chemical and genetic approach for the generation of induced pluripotent stem cells. , 2008, Cell stem cell.

[16]  Kavitha T. Kuppusamy,et al.  Hypoxia-inducible factors have distinct and stage-specific roles during reprogramming of human cells to pluripotency. , 2014, Cell stem cell.

[17]  R. Tjian,et al.  Unexpected roles for core promoter recognition factors in cell-type-specific transcription and gene regulation , 2010, Nature Reviews Genetics.

[18]  Hong Wang,et al.  The Combination of Tet1 with Oct4 Generates High‐Quality Mouse‐Induced Pluripotent Stem Cells , 2015, Stem cells.

[19]  Haitao Wu,et al.  Class IIa Histone Deacetylases and Myocyte Enhancer Factor 2 Proteins Regulate the Mesenchymal-to-Epithelial Transition of Somatic Cell Reprogramming* , 2013, The Journal of Biological Chemistry.

[20]  B. Blencowe,et al.  Myc and SAGA rewire an alternative splicing network during early somatic cell reprogramming , 2015, Genes & development.

[21]  I. Sancho-Martinez,et al.  Reprogramming of human fibroblasts to pluripotency with lineage specifiers. , 2013, Cell stem cell.

[22]  D. Pei,et al.  Vitamin C improves the quality of somatic cell reprogramming , 2012, Nature Genetics.

[23]  Michael B. Eisen,et al.  Control of Embryonic Stem Cell Lineage Commitment by Core Promoter Factor, TAF3 , 2011, Cell.

[24]  A. Radzisheuskaya,et al.  MBD3/NuRD Facilitates Induction of Pluripotency in a Context-Dependent Manner , 2014, Cell stem cell.

[25]  Mitsugu Sekimoto,et al.  Reprogramming of mouse and human cells to pluripotency using mature microRNAs. , 2011, Cell stem cell.

[26]  Wange Lu,et al.  Klf4 organizes long-range chromosomal interactions with the oct4 locus in reprogramming and pluripotency. , 2013, Cell stem cell.

[27]  S. Yamanaka,et al.  Global splicing pattern reversion during somatic cell reprogramming. , 2013, Cell reports.

[28]  Austin G Smith,et al.  Signalling, cell cycle and pluripotency in embryonic stem cells. , 2002, Trends in cell biology.

[29]  G. Bhagat,et al.  Early-stage epigenetic modification during somatic cell reprogramming by Parp1 and Tet2 , 2012, Nature.

[30]  S. Yamanaka,et al.  Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors , 2006, Cell.

[31]  J. McPherson,et al.  Antioxidant Supplementation Reduces Genomic Aberrations in Human Induced Pluripotent Stem Cells , 2014, Stem cell reports.

[32]  Oscar H. Ocaña,et al.  Epithelial plasticity, stemness and pluripotency , 2010, Cell Research.

[33]  M. Pellegrini,et al.  Pioneer Transcription Factors Target Partial DNA Motifs on Nucleosomes to Initiate Reprogramming , 2015, Cell.

[34]  Jieying Zhu,et al.  H3K9 methylation is a barrier during somatic cell reprogramming into iPSCs , 2012, Nature Genetics.

[35]  K. Hochedlinger,et al.  Chromatin dynamics during cellular reprogramming , 2013, Nature.

[36]  H. Otu,et al.  Histone chaperone ASF1A is required for maintenance of pluripotency and cellular reprogramming , 2014, Science.

[37]  Juan Carlos Izpisua Belmonte,et al.  A High Proliferation Rate Is Required for Cell Reprogramming and Maintenance of Human Embryonic Stem Cell Identity , 2011, Current Biology.

[38]  Jennifer Nichols,et al.  Promotion of Reprogramming to Ground State Pluripotency by Signal Inhibition , 2008, PLoS biology.

[39]  J. Hua,et al.  PRMT5 enhances generation of induced pluripotent stem cells from dairy goat embryonic fibroblasts via down‐regulation of p53 , 2015, Cell proliferation.

[40]  Sheng Ding,et al.  Reprogramming fibroblasts toward cardiomyocytes, neural stem cells and hepatocytes by cell activation and signaling-directed lineage conversion , 2015, Nature Protocols.

[41]  C. Chen,et al.  Manipulation of KLF4 Expression Generates iPSCs Paused at Successive Stages of Reprogramming , 2014, Stem cell reports.

[42]  J. Gil,et al.  Induced pluripotent stem cells and senescence: learning the biology to improve the technology , 2010, EMBO reports.

[43]  Leighton J. Core,et al.  Regulating RNA polymerase pausing and transcription elongation in embryonic stem cells. , 2011, Genes & development.

[44]  W. Liu,et al.  Tet and TDG mediate DNA demethylation essential for mesenchymal-to-epithelial transition in somatic cell reprogramming. , 2014, Cell stem cell.

[45]  H. Schöler,et al.  Reprogramming fibroblasts into induced pluripotent stem cells with Bmi1 , 2011, Cell Research.

[46]  R. Stewart,et al.  Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells , 2007, Science.

[47]  Marcos J. Araúzo-Bravo,et al.  Chromatin-Remodeling Components of the BAF Complex Facilitate Reprogramming , 2010, Cell.

[48]  Xiang Li,et al.  Small-Molecule-Driven Direct Reprogramming of Mouse Fibroblasts into Functional Neurons. , 2015, Cell stem cell.

[49]  S. Ramaswamy,et al.  A Molecular Roadmap of Reprogramming Somatic Cells into iPS Cells , 2012, Cell.

[50]  Muneef Ayyash,et al.  The H3K27 demethylase Utx regulates somatic and germ cell epigenetic reprogramming , 2012, Nature.

[51]  Zhiming He,et al.  Apoptotic caspases regulate induction of iPSCs from human fibroblasts. , 2010, Cell stem cell.

[52]  Yidong Chen,et al.  Jmjd3 Inhibits Reprogramming by Upregulating Expression of INK4a/Arf and Targeting PHF20 for Ubiquitination , 2013, Cell.

[53]  S. Linnarsson,et al.  High resolution analysis with novel cell-surface markers identifies routes to iPS cells , 2013, Nature.

[54]  D. Pei,et al.  MicroRNAs in somatic cell reprogramming. , 2013, Current opinion in cell biology.

[55]  W. Reik,et al.  Nanog-dependent function of Tet1 and Tet2 in establishment of pluripotency , 2013, Nature.

[56]  Jignesh R. Parikh,et al.  Alternative splicing of MBD2 supports self-renewal in human pluripotent stem cells. , 2014, Cell stem cell.

[57]  N. D. Clarke,et al.  Integration of External Signaling Pathways with the Core Transcriptional Network in Embryonic Stem Cells , 2008, Cell.

[58]  G. Pan,et al.  The histone demethylases Jhdm1a/1b enhance somatic cell reprogramming in a vitamin-C-dependent manner. , 2011, Cell stem cell.

[59]  Yi Zhang,et al.  Genetic and epigenetic variations in iPSCs: potential causes and implications for application. , 2013, Cell stem cell.

[60]  L. Zender,et al.  Activation and repression by oncogenic MYC shape tumour-specific gene expression profiles , 2014, Nature.

[61]  Shwu‐Yuan Wu,et al.  The Double Bromodomain-containing Chromatin Adaptor Brd4 and Transcriptional Regulation* , 2007, Journal of Biological Chemistry.

[62]  Andrew C. Adey,et al.  Multiplex single-cell profiling of chromatin accessibility by combinatorial cellular indexing , 2015, Science.

[63]  Jun Wang,et al.  Transcriptional pause release is a rate-limiting step for somatic cell reprogramming. , 2014, Cell stem cell.

[64]  G. Daley,et al.  Metabolic regulation in pluripotent stem cells during reprogramming and self-renewal. , 2012, Cell stem cell.

[65]  De-Pei Liu,et al.  Sox2 Deacetylation by Sirt1 Is Involved in Mouse Somatic Reprogramming , 2015, Stem cells.

[66]  Zohar Mukamel,et al.  Deterministic direct reprogramming of somatic cells to pluripotency , 2013, Nature.

[67]  P. Robson,et al.  Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm , 2013, The EMBO journal.

[68]  A. Tanay,et al.  Single cell Hi-C reveals cell-to-cell variability in chromosome structure , 2013, Nature.

[69]  T. Cai,et al.  Replacement of Oct4 by Tet1 during iPSC induction reveals an important role of DNA methylation and hydroxymethylation in reprogramming. , 2013, Cell stem cell.

[70]  Ori Bar-Nur,et al.  Lineage conversion induced by pluripotency factors involves transient passage through an iPS cell stage , 2015, Nature Biotechnology.

[71]  Hyun-Jai Cho,et al.  Induction of pluripotent stem cells from adult somatic cells by protein-based reprogramming without genetic manipulation. , 2010, Blood.

[72]  Wendy Y. Zhang,et al.  The Role of SIRT6 Protein in Aging and Reprogramming of Human Induced Pluripotent Stem Cells* , 2013, The Journal of Biological Chemistry.

[73]  Jialiang Liang,et al.  A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts. , 2010, Cell stem cell.

[74]  Christopher B. Burge,et al.  c-Myc Regulates Transcriptional Pause Release , 2010, Cell.

[75]  Francesco Ferrari,et al.  Genome-wide chromatin interactions of the Nanog locus in pluripotency, differentiation, and reprogramming. , 2013, Cell stem cell.

[76]  Zakary S. Singer,et al.  Single-cell transcriptome analysis reveals dynamic changes in lncRNA expression during reprogramming. , 2015, Cell stem cell.

[77]  S. Bonhoeffer,et al.  Cooperation and Competition in the Evolution of ATP-Producing Pathways , 2001, Science.

[78]  M. Donohoe,et al.  The BET Family Member BRD4 Interacts with OCT4 and Regulates Pluripotency Gene Expression , 2015, Stem cell reports.

[79]  Eric S. Lander,et al.  Dissecting direct reprogramming through integrative genomic analysis , 2008, Nature.

[80]  A. Nagy,et al.  Sirtuin 1 Facilitates Generation of Induced Pluripotent Stem Cells from Mouse Embryonic Fibroblasts through the miR-34a and p53 Pathways , 2012, PloS one.

[81]  Eric T. Wang,et al.  MBNL proteins repress ES-cell-specific alternative splicing and reprogramming , 2013, Nature.

[82]  Marius Wernig,et al.  Early reprogramming regulators identified by prospective isolation and mass cytometry , 2015, Nature.

[83]  Sheng Ding,et al.  Chemical approaches to stem cell biology and therapeutics. , 2013, Cell stem cell.

[84]  E. Wanker,et al.  HIF1α Modulates Cell Fate Reprogramming Through Early Glycolytic Shift and Upregulation of PDK1–3 and PKM2 , 2014, Stem cells.

[85]  B. Garcia,et al.  Proteomic and genomic approaches reveal critical functions of H3K9 methylation and Heterochromatin Protein-1γ in reprogramming to pluripotency , 2013, Nature Cell Biology.

[86]  P. Flicek,et al.  Molecular maps of the reorganization of genome-nuclear lamina interactions during differentiation. , 2010, Molecular cell.

[87]  Denis Thieffry,et al.  C/EBPα poises B cells for rapid reprogramming into induced pluripotent stem cells , 2013, Nature.

[88]  Peter A. Jones.  Functions of DNA methylation: islands, start sites, gene bodies and beyond , 2012, Nature Reviews Genetics.

[89]  K. Shirahige,et al.  Histone variants enriched in oocytes enhance reprogramming to induced pluripotent stem cells. , 2014, Cell stem cell.

[90]  G. Jayandharan,et al.  Ezh2 mediated H3K27me3 activity facilitates somatic transition during human pluripotent reprogramming , 2015, Scientific Reports.

[91]  J. Carroll,et al.  Pioneer transcription factors: establishing competence for gene expression. , 2011, Genes & development.

[92]  Jing Liu,et al.  Towards an Optimized Culture Medium for the Generation of Mouse Induced Pluripotent Stem Cells* , 2010, The Journal of Biological Chemistry.

[93]  J. I. Izpisúa Belmonte,et al.  Macrohistone variants preserve cell identity by preventing the gain of H3K4me2 during reprogramming to pluripotency. , 2013, Cell reports.

[94]  D. Covas,et al.  Pluripotent reprogramming of fibroblasts by lentiviral mediated insertion of SOX2, C-MYC, and TCL-1A. , 2011, Stem cells and development.

[95]  W. Wong,et al.  Activation of Innate Immunity Is Required for Efficient Nuclear Reprogramming , 2012, Cell.

[96]  Jeffrey L. Wrana,et al.  An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming , 2011, Cell.

[97]  O. Elemento,et al.  AID stabilizes stem cell phenotype by removing epigenetic memory of pluripotency genes , 2013, Nature.

[98]  K. Reddy,et al.  Genome regulation at the peripheral zone: lamina associated domains in development and disease. , 2014, Current opinion in genetics & development.

[99]  David A. Orlando,et al.  Mediator and Cohesin Connect Gene Expression and Chromatin Architecture , 2010, Nature.

[100]  Yuriy L Orlov,et al.  The nuclear receptor Nr5a2 can replace Oct4 in the reprogramming of murine somatic cells to pluripotent cells. , 2010, Cell stem cell.

[101]  Jialei Hu,et al.  Reprogramming of mouse and human somatic cells by high‐performance engineered factors , 2011, EMBO reports.

[102]  B. Ren,et al.  The 3D genome in transcriptional regulation and pluripotency. , 2014, Cell stem cell.

[103]  David A. Orlando,et al.  Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes , 2013, Cell.

[104]  Sandy L. Klemm,et al.  Single-Cell Expression Analyses during Cellular Reprogramming Reveal an Early Stochastic and a Late Hierarchic Phase , 2012, Cell.

[105]  B. Garcia,et al.  MacroH2A histone variants act as a barrier upon reprogramming towards pluripotency , 2013, Nature Communications.

[106]  G. Pan,et al.  Vitamin C modulates TET1 function during somatic cell reprogramming , 2013, Nature Genetics.

[107]  Raja Jothi,et al.  INO80 facilitates pluripotency gene activation in embryonic stem cell self-renewal, reprogramming, and blastocyst development. , 2014, Cell stem cell.

[108]  W. Birchmeier,et al.  E‐cadherin is crucial for embryonic stem cell pluripotency and can replace OCT4 during somatic cell reprogramming , 2011, EMBO reports.

[109]  Zachary D. Smith,et al.  Reprogramming factor expression initiates widespread targeted chromatin remodeling. , 2011, Cell stem cell.

[110]  C. Pereira,et al.  Senescence impairs successful reprogramming to pluripotent stem cells. , 2009, Genes & development.

[111]  M. Surani,et al.  Histone variant macroH2A marks embryonic differentiation in vivo and acts as an epigenetic barrier to induced pluripotency , 2012, Journal of Cell Science.

[112]  Dong Wook Han,et al.  A central role for TFIID in the pluripotent transcription circuitry , 2013, Nature.

[113]  Michael T. McManus,et al.  Systematic Identification of Barriers to Human iPSC Generation , 2014, Cell.

[114]  H. Blau,et al.  A critical role for AID in the initiation of reprogramming to induced pluripotent stem cells , 2013, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[115]  Jiuhong Kang,et al.  An HDAC2-TET1 switch at distinct chromatin regions significantly promotes the maturation of pre-iPS to iPS cells , 2015, Nucleic acids research.

[116]  A. Tsirigos,et al.  Combinatorial Modulation of Signaling Pathways Reveals Cell-Type-Specific Requirements for Highly Efficient and Synchronous iPSC Reprogramming , 2014, Stem cell reports.

[117]  A. Consiglio,et al.  Rem2 GTPase maintains survival of human embryonic stem cells as well as enhancing reprogramming by regulating p53 and cyclin D1. , 2010, Genes & development.

[118]  Matteo Pellegrini,et al.  Long-range chromatin contacts in embryonic stem cells reveal a role for pluripotency factors and polycomb proteins in genome organization. , 2013, Cell stem cell.

[119]  Xin Xie,et al.  Bromodeoxyuridine promotes full-chemical induction of mouse pluripotent stem cells , 2015, Cell Research.

[120]  Hsin-Yang Li,et al.  CHD1L Regulated PARP1‐Driven Pluripotency and Chromatin Remodeling During the Early‐Stage Cell Reprogramming , 2015, Stem cells.

[121]  F. Wang,et al.  Influences of lamin A levels on induction of pluripotent stem cells , 2012, Biology Open.

[122]  David L. A. Wood,et al.  Divergent reprogramming routes lead to alternative stem-cell states , 2014, Nature.

[123]  Hiroyuki Hirai,et al.  Radical Acceleration of Nuclear Reprogramming by Chromatin Remodeling with the Transactivation Domain of MyoD , 2011, Stem cells.

[124]  G. Wahl,et al.  Linking the p53 tumor suppressor pathway to somatic cell reprogramming , 2009, Nature.

[125]  Rudolf Jaenisch,et al.  Mechanisms and models of somatic cell reprogramming , 2013, Nature Reviews Genetics.

[126]  H. Broxmeyer,et al.  Epigenetic Regulation of Nanog by MiR‐302 Cluster‐MBD2 Completes Induced Pluripotent Stem Cell Reprogramming , 2013, Stem cells.

[127]  H. Deng,et al.  Pluripotent Stem Cells Induced from Mouse Somatic Cells by Small-Molecule Compounds , 2013, Science.

[128]  H. Redl,et al.  Vitamin C enhances the generation of mouse and human induced pluripotent stem cells. , 2010, Cell stem cell.

[129]  I. Grummt,et al.  NuRD Blocks Reprogramming of Mouse Somatic Cells into Pluripotent Stem Cells , 2013, Stem cells.

[130]  Gangning Liang,et al.  Polycomb-Repressed Genes Have Permissive Enhancers that Initiate Reprogramming , 2011, Cell.

[131]  Howard Y. Chang,et al.  The histone chaperone CAF-1 safeguards somatic cell identity , 2015, Nature.

[132]  Qi Sun,et al.  Interaction with WDR5 promotes target gene recognition and tumorigenesis by MYC. , 2015, Molecular cell.

[133]  Rong Wang,et al.  Coordination of m(6)A mRNA Methylation and Gene Transcription by ZFP217 Regulates Pluripotency and Reprogramming. , 2015, Cell stem cell.

[134]  Mudit Gupta,et al.  Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. , 2011, Cell stem cell.

[135]  H. Tse,et al.  The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters , 2014, Cell Research.

[136]  Ru Zhang,et al.  Proliferation Rate of Somatic Cells Affects Reprogramming Efficiency , 2013, The Journal of Biological Chemistry.

[137]  C. Lengner,et al.  Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells. , 2008, Cell stem cell.

[138]  K. Hochedlinger,et al.  Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. , 2008, Cell stem cell.

[139]  Yoshifumi Kawamura,et al.  Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1 , 2011, Nature.

[140]  J. Shu,et al.  Induction of Pluripotency in Mouse Somatic Cells with Lineage Specifiers , 2013, Cell.

[141]  K. Hochedlinger,et al.  Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells , 2010, Nature Biotechnology.

[142]  G. Pan,et al.  The oncogene c-Jun impedes somatic cell reprogramming , 2015, Nature Cell Biology.

[143]  Qi Zhou,et al.  m(6)A RNA methylation is regulated by microRNAs and promotes reprogramming to pluripotency. , 2015, Cell stem cell.

[144]  TangYong,et al.  Knockdown of Brm and Baf170, Components of Chromatin Remodeling Complex, Facilitates Reprogramming of Somatic Cells. , 2015 .

[145]  M. Araúzo-Bravo,et al.  Direct reprogramming of fibroblasts into epiblast stem cells , 2011, Nature Cell Biology.

[146]  Mike J. Mason,et al.  Role of the Murine Reprogramming Factors in the Induction of Pluripotency , 2009, Cell.

[147]  I. Wilmut,et al.  Nuclear transfer to eggs and oocytes. , 2011, Cold Spring Harbor perspectives in biology.

[148]  Dong Wook Han,et al.  Generation of induced pluripotent stem cells using recombinant proteins. , 2009, Cell stem cell.

[149]  Helen M. Blau,et al.  Reprogramming towards pluripotency requires AID-dependent DNA demethylation , 2010, Nature.

[150]  Takashi Aoi,et al.  Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts , 2008, Nature Biotechnology.

[151]  Eric S. Lander,et al.  Chromatin modifying enzymes as modulators of reprogramming , 2012, Nature.

[152]  J. Wrana,et al.  Functional genomics reveals a BMP-driven mesenchymal-to-epithelial transition in the initiation of somatic cell reprogramming. , 2010, Cell stem cell.

[153]  A. Fatica,et al.  Long non-coding RNAs: new players in cell differentiation and development , 2013, Nature Reviews Genetics.

[154]  Wei Wang,et al.  piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells , 2009, Nature.

[155]  Greg Donahue,et al.  Facilitators and Impediments of the Pluripotency Reprogramming Factors' Initial Engagement with the Genome , 2012, Cell.

[156]  O. Stegle,et al.  Single-Cell Genome-Wide Bisulfite Sequencing for Assessing Epigenetic Heterogeneity , 2014, Nature Methods.

[157]  Wei Li,et al.  Intrachromosomal looping is required for activation of endogenous pluripotency genes during reprogramming. , 2013, Cell stem cell.

[158]  John T. Lis,et al.  Defining mechanisms that regulate RNA polymerase II transcription in vivo , 2009, Nature.

[159]  Jennifer A. Mitchell,et al.  Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells , 2010, Nature Genetics.

[160]  Thomas Lufkin,et al.  Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb , 2009, Nature Cell Biology.

[161]  Shaorong Gao,et al.  RCOR2 Is a Subunit of the LSD1 Complex That Regulates ESC Property and Substitutes for SOX2 in Reprogramming Somatic Cells to Pluripotency , 2011, Stem cells.

[162]  Jonathan M. Monk,et al.  Wdr5 Mediates Self-Renewal and Reprogramming via the Embryonic Stem Cell Core Transcriptional Network , 2011, Cell.

[163]  S. Orkin,et al.  An Extended Transcriptional Network for Pluripotency of Embryonic Stem Cells , 2008, Cell.

[164]  Marco J. Morelli,et al.  Selective transcriptional regulation by Myc in cellular growth control and lymphomagenesis , 2014, Nature.

[165]  S. G. Cheng,et al.  c-MYC interacts with INI1/hSNF5 and requires the SWI/SNF complex for transactivation function , 1999, Nature Genetics.

[166]  Ning Leng,et al.  Collaborative rewiring of the pluripotency network by chromatin and signalling modulating pathways , 2015, Nature Communications.

[167]  Yi Zhang,et al.  Kdm2b promotes induced pluripotent stem cell generation by facilitating gene activation early in reprogramming , 2012, Nature Cell Biology.

[168]  Michael J. Ziller,et al.  Integrative Analyses of Human Reprogramming Reveal Dynamic Nature of Induced Pluripotency , 2015, Cell.