Mechanisms and models of somatic cell reprogramming Citation

Conversion of somatic cells to pluripotency by defined factors is a long and complex process that yields embryonic stem cell-like cells that vary in their developmental potential. To improve the quality of resulting induced pluripotent stem cells (iPSCs), which is important for potential therapeutic applications, and to address fundamental questions about control of cell identity, molecular mechanisms of the reprogramming process must be understood. Here we discuss recent discoveries regarding the role of reprogramming factors in remodeling the genome, including new insights into the function of c-Myc, and describe the different phases, markers and emerging models of reprogramming.

[1]  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.

[2]  T. Ludwig,et al.  Homologous recombination DNA repair genes play a critical role in reprogramming to a pluripotent state. , 2013, Cell reports.

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

[4]  Bradley E. Bernstein,et al.  Genome-wide Chromatin State Transitions Associated with Developmental and Environmental Cues , 2013, Cell.

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

[6]  Alexander S. Garruss,et al.  The RNA Pol II Elongation Factor Ell3 Marks Enhancers in ES Cells and Primes Future Gene Activation , 2013, Cell.

[7]  I. Sancho-Martinez,et al.  Stem cells: Surf the waves of reprogramming , 2013, Nature.

[8]  S. Seneca,et al.  Human embryonic stem cells commonly display large mitochondrial DNA deletions , 2013, Nature Biotechnology.

[9]  M. Dezawa,et al.  The elite and stochastic model for iPS cell generation: Multilineage‐differentiating stress enduring (Muse) cells are readily reprogrammable into iPS cells , 2013, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[10]  Jeroen Krijgsveld,et al.  Highly coordinated proteome dynamics during reprogramming of somatic cells to pluripotency. , 2012, Cell reports.

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

[12]  Yi Zhang,et al.  Embryonic stem cell and induced pluripotent stem cell: an epigenetic perspective , 2012, Cell Research.

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

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

[15]  Rudolf Jaenisch,et al.  Nuclear cloning and direct reprogramming: the long and the short path to Stockholm. , 2012, Cell stem cell.

[16]  Frank Soldner,et al.  iPSC Disease Modeling , 2012, Science.

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

[18]  R. Jaenisch,et al.  Transdifferentiation by defined factors as a powerful research tool to address basic biological questions , 2012, Cell cycle.

[19]  Hui Yang,et al.  Zscan4 promotes genomic stability during reprogramming and dramatically improves the quality of iPS cells as demonstrated by tetraploid complementation , 2012, Cell Research.

[20]  M. Gerstein,et al.  Somatic copy-number mosaicism in human skin revealed by induced pluripotent stem cells , 2012, Nature.

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

[22]  Abdulrahim A. Sajini,et al.  Analysis of endogenous Oct4 activation during induced pluripotent stem cell reprogramming using an inducible Oct4 lineage label. , 2012, Stem cells.

[23]  K. Plath,et al.  The roles of the reprogramming factors Oct4, Sox2 and Klf4 in resetting the somatic cell epigenome during induced pluripotent stem cell generation , 2012, Genome Biology.

[24]  Charles Y. Lin,et al.  Transcriptional Amplification in Tumor Cells with Elevated c-Myc , 2012, Cell.

[25]  D. Green,et al.  c-Myc Is a Universal Amplifier of Expressed Genes in Lymphocytes and Embryonic Stem Cells , 2012, Cell.

[26]  Thomas Vierbuchen,et al.  Molecular roadblocks for cellular reprogramming. , 2012, Molecular cell.

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

[28]  J. Dekker,et al.  The long-range interaction landscape of gene promoters , 2012, Nature.

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

[30]  Alan Mackay-Sim,et al.  Variability in the Generation of Induced Pluripotent Stem Cells: Importance for Disease Modeling , 2012, Stem cells translational medicine.

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

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

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

[34]  Chi V Dang,et al.  MYC on the Path to Cancer , 2012, Cell.

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

[36]  P. Park,et al.  Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of all-iPS cell mice from terminally differentiated B cells , 2012, Nature Genetics.

[37]  Yutao Du,et al.  Low incidence of DNA sequence variation in human induced pluripotent stem cells generated by nonintegrating plasmid expression. , 2012, Cell stem cell.

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

[39]  Marius Wernig,et al.  Comprehensive qPCR profiling of gene expression in single neuronal cells , 2011, Nature Protocols.

[40]  Rudolf Jaenisch,et al.  Reprogramming factor stoichiometry influences the epigenetic state and biological properties of induced pluripotent stem cells. , 2011, Cell stem cell.

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

[42]  Eran Meshorer,et al.  Global epigenetic changes during somatic cell reprogramming to iPS cells. , 2011, Journal of molecular cell biology.

[43]  Andrew P. Feinberg,et al.  Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells , 2011, Nature Biotechnology.

[44]  Jennifer M. Bolin,et al.  Proteomic and phosphoproteomic comparison of human ES and iPS cells , 2011, Nature Methods.

[45]  N. Benvenisty,et al.  Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells. , 2011, Cell stem cell.

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

[47]  H. Schöler,et al.  Optimal reprogramming factor stoichiometry increases colony numbers and affects molecular characteristics of murine induced pluripotent stem cells , 2011, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[48]  C. Perez-Iratxeta,et al.  Constitutive heterochromatin reorganization during somatic cell reprogramming , 2011, The EMBO journal.

[49]  Robert L. Judson,et al.  Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cells , 2011, Nature Biotechnology.

[50]  Jun S. Song,et al.  Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells , 2011, Nature Cell Biology.

[51]  S. Lipton,et al.  Direct reprogramming of mouse fibroblasts to neural progenitors , 2011, Proceedings of the National Academy of Sciences.

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

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

[54]  J. Chen,et al.  Rational optimization of reprogramming culture conditions for the generation of induced pluripotent stem cells with ultra-high efficiency and fast kinetics , 2011, Cell Research.

[55]  Maikun Teng,et al.  MicroRNA Cluster 302–367 Enhances Somatic Cell Reprogramming by Accelerating a Mesenchymal-to-Epithelial Transition* , 2011, The Journal of Biological Chemistry.

[56]  R. Stewart,et al.  Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells , 2011, Nature.

[57]  Riitta Lahesmaa,et al.  Copy number variation and selection during reprogramming to pluripotency , 2011, Nature.

[58]  Jarrett Rosenberg,et al.  Single cell transcriptional profiling reveals heterogeneity of human induced pluripotent stem cells. , 2011, The Journal of clinical investigation.

[59]  T. Tada,et al.  Sox2 expression effects on direct reprogramming efficiency as determined by alternative somatic cell fate. , 2011, Stem cell research.

[60]  Gang Wang,et al.  Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy , 2011, Nature Cell Biology.

[61]  Qi Zhou,et al.  Brief Report: Combined Chemical Treatment Enables Oct4‐Induced Reprogramming from Mouse Embryonic Fibroblasts , 2011, Stem cells.

[62]  Michael J. Ziller,et al.  Reference Maps of Human ES and iPS Cell Variation Enable High-Throughput Characterization of Pluripotent Cell Lines , 2011, Cell.

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

[64]  Julie V. Harness,et al.  Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and iPSCs during reprogramming and time in culture. , 2011, Cell stem cell.

[65]  Mark Ellisman,et al.  Mitochondrial Rejuvenation After Induced Pluripotency , 2010, PloS one.

[66]  K. Hochedlinger,et al.  Induced pluripotency: history, mechanisms, and applications. , 2010, Genes & development.

[67]  Yoav Mayshar,et al.  Identification and classification of chromosomal aberrations in human induced pluripotent stem cells. , 2010, Cell stem cell.

[68]  Richard A Young,et al.  Chromatin structure and gene expression programs of human embryonic and induced pluripotent stem cells. , 2010, Cell stem cell.

[69]  Aaron M. Newman,et al.  Lab-specific gene expression signatures in pluripotent stem cells. , 2010, Cell stem cell.

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

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

[72]  Shinsuke Yuasa,et al.  Generation of induced pluripotent stem cells from human terminally differentiated circulating T cells. , 2010, Cell stem cell.

[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]  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.

[75]  Martin J. Aryee,et al.  Epigenetic memory in induced pluripotent stem cells , 2010, Nature.

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

[77]  H. Blau,et al.  Nuclear reprogramming to a pluripotent state by three approaches , 2010, Nature.

[78]  Tomohiro Kono,et al.  Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells , 2010, Nature.

[79]  Jennifer A. Erwin,et al.  Derivation of Pre-X Inactivation Human Embryonic Stem Cells under Physiological Oxygen Concentrations , 2010, Cell.

[80]  Zachary D. Smith,et al.  Dynamic single-cell imaging of direct reprogramming reveals an early specifying event , 2010, Nature Biotechnology.

[81]  Qi Zhou,et al.  Production of mice using iPS cells and tetraploid complementation , 2010, Nature Protocols.

[82]  Mikael Huss,et al.  Resolution of cell fate decisions revealed by single-cell gene expression analysis from zygote to blastocyst. , 2010, Developmental cell.

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

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

[85]  Ryoko Araki,et al.  Conversion of Ancestral Fibroblasts to Induced Pluripotent Stem Cells , 2009, Stem cells.

[86]  Martin J Aryee,et al.  Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts , 2009, Nature Genetics.

[87]  David R. Liu,et al.  A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog. , 2009, Cell stem cell.

[88]  K. Hochedlinger,et al.  Tgfβ Signal Inhibition Cooperates in the Induction of iPSCs and Replaces Sox2 and cMyc , 2009, Current Biology.

[89]  Jeroen S. van Zon,et al.  Direct cell reprogramming is a stochastic process amenable to acceleration , 2009, Nature.

[90]  Shaorong Gao,et al.  Cell Stem Cell Brief Report Ips Cells Can Support Full-term Development of Tetraploid Blastocyst-complemented Embryos Cell Stem Cell Brief Report , 2022 .

[91]  Qi Zhou,et al.  iPS cells produce viable mice through tetraploid complementation , 2009, Nature.

[92]  A. Hoffmann,et al.  A Unifying Model for the Selective Regulation of Inducible Transcription by CpG Islands and Nucleosome Remodeling , 2009, Cell.

[93]  Shinya Yamanaka,et al.  Elite and stochastic models for induced pluripotent stem cell generation , 2009, Nature.

[94]  Mike J. Mason,et al.  Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. , 2009, Cell stem cell.

[95]  Benoit G. Bruneau,et al.  Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors , 2009, Nature.

[96]  Irving L. Weissman,et al.  Association of reactive oxygen species levels and radioresistance in cancer stem cells , 2009, Nature.

[97]  G. Lewin,et al.  Supplemental Figure S1 , 2021 .

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

[99]  L. Penn,et al.  Reflecting on 25 years with MYC , 2008, Nature Reviews Cancer.

[100]  R. Eisenman,et al.  Myc's broad reach. , 2008, Genes & development.

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

[102]  Scott A. Rifkin,et al.  Imaging individual mRNA molecules using multiple singly labeled probes , 2008, Nature Methods.

[103]  Clifford A. Meyer,et al.  Model-based Analysis of ChIP-Seq (MACS) , 2008, Genome Biology.

[104]  Takashi Aoi,et al.  Generation of Pluripotent Stem Cells from Adult Mouse Liver and Stomach Cells , 2008, Science.

[105]  T. Mikkelsen,et al.  Dissecting direct reprogramming through integrative genomic analysis , 2008, Nature.

[106]  Wenjun Guo,et al.  Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds , 2008, Nature Biotechnology.

[107]  C. Lengner,et al.  Direct Reprogramming of Terminally Differentiated Mature B Lymphocytes to Pluripotency , 2008, Cell.

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

[109]  R. Young,et al.  Stem Cells, the Molecular Circuitry of Pluripotency and Nuclear Reprogramming , 2008, Cell.

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

[111]  Marius Wernig,et al.  Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells , 2007, Nature Biotechnology.

[112]  J. Utikal,et al.  Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. , 2007, Cell stem cell.

[113]  E. Lander,et al.  The Mammalian Epigenome , 2007, Cell.

[114]  S. Nishikawa,et al.  Equivalency of Nuclear Transfer‐Derived Embryonic Stem Cells to Those Derived from Fertilized Mouse Blastocysts , 2006, Stem cells.

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

[116]  R. Jaenisch,et al.  ES cells derived from cloned and fertilized blastocysts are transcriptionally and functionally indistinguishable. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[117]  Megan F. Cole,et al.  Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells , 2005, Cell.

[118]  R. Medema,et al.  Myc‐induced proliferation and transformation require Akt‐mediated phosphorylation of FoxO proteins , 2004, The EMBO journal.

[119]  G. Schotta,et al.  SU(VAR)3-9 is a Conserved Key Function in Heterochromatic Gene Silencing , 2003, Genetica.

[120]  R. Jaenisch,et al.  Monoclonal mice generated by nuclear transfer from mature B and T donor cells , 2002, Nature.

[121]  P. Farnham,et al.  c-Myc Mediates Activation of the cad Promoter via a Post-RNA Polymerase II Recruitment Mechanism* , 2001, The Journal of Biological Chemistry.

[122]  E. Pennisi,et al.  Will Dolly Send in the Clones? , 1997, Science.

[123]  J. Gurdon,et al.  Efficiencies and mechanisms of nuclear reprogramming. , 2010, Cold Spring Harbor symposia on quantitative biology.

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

[125]  G. Galbraith,et al.  In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state , 2008 .

[126]  B. Thiers Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors , 2008 .

[127]  T. Misteli,et al.  Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells. , 2006, Developmental cell.

[128]  R. Eisenman,et al.  Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. , 1991, Science.