Molecular Cell Resource Dynamic Heterogeneity and DNA Methylation in Embryonic Stem Cells

Zakary S. Singer,1,7 John Yong,2,7 Julia Tischler,6 Jamie A. Hackett,6 Alphan Altinok,2,3 M. Azim Surani,6 Long Cai,4 and Michael B. Elowitz5,* 1Computation and Neural Systems 2Division of Biology 3Biological Network Modeling Center 4Program in Biochemistry and Molecular Biophysics and Division of Chemistry and Chemical Engineering 5Howard Hughes Medical Institute and Division of Biology and Department of Applied Physics California Institute of Technology, Pasadena, CA 91125, USA 6The Wellcome Trust/Cancer Research UK Gurdon Institute, The Henry Wellcome Building of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK 7Co-first author *Correspondence: melowitz@caltech.edu http://dx.doi.org/10.1016/j.molcel.2014.06.029

[1]  Timur Zhiyentayev,et al.  Single-cell in situ RNA profiling by sequential hybridization , 2014, Nature Methods.

[2]  I. Amit,et al.  Massively Parallel Single-Cell RNA-Seq for Marker-Free Decomposition of Tissues into Cell Types , 2014, Science.

[3]  Panteleimon Rompolas,et al.  Spatial organization within a niche as a determinant of stem cell fate , 2013, Nature.

[4]  M. Gut,et al.  Whole-genome bisulfite sequencing of two distinct interconvertible DNA methylomes of mouse embryonic stem cells. , 2013, Cell stem cell.

[5]  A. van Oudenaarden,et al.  Allele-specific detection of single mRNA molecules in situ , 2013, Nature Methods.

[6]  Hao Yuan Kueh,et al.  Positive Feedback Between PU.1 and the Cell Cycle Controls Myeloid Differentiation , 2013, Science.

[7]  W. Reik,et al.  FGF Signaling Inhibition in ESCs Drives Rapid Genome-wide Demethylation to the Epigenetic Ground State of Pluripotency , 2013, Clinical Epigenetics.

[8]  Heiko Lickert,et al.  Biallelic expression of nanog protein in mouse embryonic stem cells. , 2013, Cell stem cell.

[9]  R. Jaenisch,et al.  Single-cell analysis reveals that expression of nanog is biallelic and equally variable as that of other pluripotency factors in mouse ESCs. , 2013, Cell stem cell.

[10]  F. Tang,et al.  Prdm14 promotes germline fate and naive pluripotency by repressing FGF signalling and DNA methylation , 2013, EMBO reports.

[11]  Rudolf Jaenisch,et al.  One-Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR/Cas-Mediated Genome Engineering , 2013, Cell.

[12]  Rona S. Gertner,et al.  Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells , 2013, Nature.

[13]  K. Shirahige,et al.  PRDM14 ensures naive pluripotency through dual regulation of signaling and epigenetic pathways in mouse embryonic stem cells. , 2013, Cell stem cell.

[14]  Kirsten R. McEwen,et al.  Naïve pluripotency is associated with global DNA hypomethylation , 2013, Nature Structural &Molecular Biology.

[15]  T. Down,et al.  Germline DNA Demethylation Dynamics and Imprint Erasure Through 5-Hydroxymethylcytosine , 2013, Science.

[16]  C. Furusawa,et al.  A Dynamical-Systems View of Stem Cell Biology , 2012, Science.

[17]  Nicola Festuccia,et al.  Esrrb Is a Direct Nanog Target Gene that Can Substitute for Nanog Function in Pluripotent Cells , 2012, Cell stem cell.

[18]  Long Cai,et al.  Single cell systems biology by super-resolution imaging and combinatorial labeling , 2012, Nature Methods.

[19]  Shawn P. Driscoll,et al.  ES cell potency fluctuates with endogenous retrovirus activity , 2012, Nature.

[20]  Jennifer Nichols,et al.  The Transcriptional and Epigenomic Foundations of Ground State Pluripotency , 2012, Cell.

[21]  Zachary D. Smith,et al.  A unique regulatory phase of DNA methylation in the early mammalian embryo , 2012, Nature.

[22]  M. Torres-Padilla,et al.  Control of ground-state pluripotency by allelic regulation of Nanog , 2012, Nature.

[23]  E. Lander,et al.  Theory Stochastic State Transitions Give Rise to Phenotypic Equilibrium in Populations of Cancer Cells , 2011 .

[24]  R. Sandberg,et al.  CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing , 2011, Nature.

[25]  Peter A. Jones,et al.  OCT4 establishes and maintains nucleosome-depleted regions that provide additional layers of epigenetic regulation of its target genes , 2011, Proceedings of the National Academy of Sciences.

[26]  Austin G Smith,et al.  Inhibition of glycogen synthase kinase-3 alleviates Tcf3 repression of the pluripotency network and increases embryonic stem cell resistance to differentiation , 2011, Nature Cell Biology.

[27]  Nacho Molina,et al.  Mammalian Genes Are Transcribed with Widely Different Bursting Kinetics , 2011, Science.

[28]  W. Reik,et al.  Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation , 2011, Nature.

[29]  Keji Zhao,et al.  Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells , 2011, Nature.

[30]  Riitta Lahesmaa,et al.  Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells. , 2011, Cell stem cell.

[31]  Anton Valouev,et al.  Sequence-specific regulator Prdm14 safeguards mouse ESCs from entering extraembryonic endoderm fates , 2011, Nature Structural &Molecular Biology.

[32]  Michael Weber,et al.  Targets and dynamics of promoter DNA methylation during early mouse development , 2010, Nature Genetics.

[33]  L. A. Sepúlveda,et al.  Lysogen stability is determined by the frequency of activity bursts from the fate-determining gene , 2010, Molecular systems biology.

[34]  M. Elowitz,et al.  Functional roles for noise in genetic circuits , 2010, Nature.

[35]  Yi Zhang,et al.  Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification , 2010, Nature.

[36]  Austin G Smith,et al.  The ground state of pluripotency. , 2010, Biochemical Society transactions.

[37]  Ingo Roeder,et al.  Nanog Variability and Pluripotency Regulation of Embryonic Stem Cells - Insights from a Mathematical Model Analysis , 2010, PloS one.

[38]  Alexei A. Sharov,et al.  Functional Heterogeneity of Embryonic Stem Cells Revealed through Translational Amplification of an Early Endodermal Transcript , 2010, PLoS biology.

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

[40]  Janet Rossant,et al.  FGF signal-dependent segregation of primitive endoderm and epiblast in the mouse blastocyst , 2010, Development.

[41]  C. Lim,et al.  Regulated Fluctuations in Nanog Expression Mediate Cell Fate Decisions in Embryonic Stem Cells , 2009, PLoS biology.

[42]  James C. W. Locke,et al.  Using movies to analyse gene circuit dynamics in single cells , 2009, Nature Reviews Microbiology.

[43]  F. Hayot,et al.  Stochasticity of gene products from transcriptional pulsing. , 2009, Physical review. E, Statistical, nonlinear, and soft matter physics.

[44]  Q. Nie,et al.  Cell Lineages and the Logic of Proliferative Control , 2009, PLoS biology.

[45]  M. Elowitz,et al.  Regulatory activity revealed by dynamic correlations in gene expression noise , 2008, Nature Genetics.

[46]  D. Larson,et al.  Single-RNA counting reveals alternative modes of gene expression in yeast , 2008, Nature Structural &Molecular Biology.

[47]  Alexei A. Sharov,et al.  Database for mRNA Half-Life of 19 977 Genes Obtained by DNA Microarray Analysis of Pluripotent and Differentiating Mouse Embryonic Stem Cells , 2008, DNA research : an international journal for rapid publication of reports on genes and genomes.

[48]  Vahid Shahrezaei,et al.  Analytical distributions for stochastic gene expression , 2008, Proceedings of the National Academy of Sciences.

[49]  F. Tang,et al.  Dynamic equilibrium and heterogeneity of mouse pluripotent stem cells with distinct functional and epigenetic states. , 2008, Cell stem cell.

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

[51]  T. Mikkelsen,et al.  Genome-scale DNA methylation maps of pluripotent and differentiated cells , 2008, Nature.

[52]  Michael B. Stadler,et al.  Lineage-specific polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors. , 2008, Molecular cell.

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

[54]  Hannah H. Chang,et al.  Transcriptome-wide noise controls lineage choice in mammalian progenitor cells , 2008, Nature.

[55]  H. Niwa,et al.  Identification and characterization of subpopulations in undifferentiated ES cell culture , 2008, Development.

[56]  Matteo Pellegrini,et al.  Promoter CpG methylation contributes to ES cell gene regulation in parallel with Oct4/Nanog, PcG complex, and histone H3 K4/K27 trimethylation. , 2008, Cell stem cell.

[57]  J. Nichols,et al.  Nanog safeguards pluripotency and mediates germline development , 2007, Nature.

[58]  N. Terada,et al.  A Heterogeneous Expression Pattern for Nanog in Embryonic Stem Cells , 2007, Stem cells.

[59]  D. Dubnau,et al.  Noise in Gene Expression Determines Cell Fate in Bacillus subtilis , 2007, Science.

[60]  W. Reik Stability and flexibility of epigenetic gene regulation in mammalian development , 2007, Nature.

[61]  Stuart H. Orkin,et al.  A protein interaction network for pluripotency of embryonic stem cells , 2006, Nature.

[62]  R. Milo,et al.  Variability and memory of protein levels in human cells , 2006, Nature.

[63]  Nir Friedman,et al.  Linking stochastic dynamics to population distribution: an analytical framework of gene expression. , 2006, Physical review letters.

[64]  Tomohiro Hayakawa,et al.  Maintenance of self‐renewal ability of mouse embryonic stem cells in the absence of DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b , 2006, Genes to cells : devoted to molecular & cellular mechanisms.

[65]  Gürol M. Süel,et al.  An excitable gene regulatory circuit induces transient cellular differentiation , 2006, Nature.

[66]  N. Friedman,et al.  Stochastic protein expression in individual cells at the single molecule level , 2006, Nature.

[67]  P. Swain,et al.  Gene Regulation at the Single-Cell Level , 2005, Science.

[68]  A. van Oudenaarden,et al.  Noise Propagation in Gene Networks , 2005, Science.

[69]  Mads Kærn,et al.  Noise in eukaryotic gene expression , 2003, Nature.

[70]  P. Swain,et al.  Stochastic Gene Expression in a Single Cell , 2002, Science.

[71]  Ertugrul M. Ozbudak,et al.  Regulation of noise in the expression of a single gene , 2002, Nature Genetics.

[72]  M. Groudine,et al.  Genomic Targeting of Methylated DNA: Influence of Methylation on Transcription, Replication, Chromatin Structure, and Histone Acetylation , 2000, Molecular and Cellular Biology.

[73]  M. Ehrenberg,et al.  Stochastic focusing: fluctuation-enhanced sensitivity of intracellular regulation. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[74]  M. Ehrenberg,et al.  Random signal fluctuations can reduce random fluctuations in regulated components of chemical regulatory networks. , 2000, Physical review letters.

[75]  D. Haber,et al.  DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De Novo Methylation and Mammalian Development , 1999, Cell.

[76]  S. Melmed,et al.  Autoregulation of pituitary corticotroph SOCS-3 expression: characterization of the murine SOCS-3 promoter. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[77]  J. Peccoud,et al.  Markovian Modeling of Gene-Product Synthesis , 1995 .

[78]  Hernan G. Garcia,et al.  Supplemental Information The Transcription Factor Titration Effect Dictates Level of Gene Expression , 2014 .

[79]  杉本 敏美,et al.  Esrrb is a pivotal target of the Gsk3/Tcf3 axis regulating embryonic stem cell self-renewal , 2012 .

[80]  D. Tranchina,et al.  Mechanistic model of bursts in mRNA synthesis , 2006 .

[81]  滝沢 琢己 DNA methylation is a critical cell-intrinsic determinant of astrocyte differentiation in the fetal brain , 2002 .

[82]  Kirsten L. Frieda,et al.  Supporting Online Material Materials and Methods Figs. S1 to S8 Tables S1 to S4 References a Stochastic Single-molecule Event Triggers Phenotype Switching of a Bacterial Cell , 2022 .