Epigenetic dynamics of stem cells and cell lineage commitment: digging Waddington's canal
Nature Reviews Molecular Cell BiologyPublished 15 July 2009
Myriam Hemberger, Wendy Dean, Wolf Reik
Citations468
SJR quartileQ1
SJR score37.35
SNIP20.23
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TL;DR
The intersection of major epigenetic reprogramming and programming events in the early embryo creates plasticity followed by commitment to the principal cell lineages of the early conceptus.
Abstract
Cells of the early mammalian embryo, including pluripotent embryonic stem (ES) cells and primordial germ cells (PGCs), are epigenetically dynamic and heterogeneous. During early development, this heterogeneity of epigenetic states is associated with stochastic expression of lineage-determining transcription factors that establish an intimate crosstalk with epigenetic modifiers. Lineage-specific epigenetic modification of crucial transcription factor loci (for example, methylation of the Elf5 promoter) leads to the restriction of transcriptional circuits and the fixation of lineage fate. The intersection of major epigenetic reprogramming and programming events in the early embryo creates plasticity followed by commitment to the principal cell lineages of the early conceptus.
Keywords
Biochemistry, Genetics and Molecular Biology
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DevelopmentMethylation levels of maternal and paternal genomes during preimplantation development
308 Citations1991Sarah Howlett, Wolf Reik
The comparison of maternal and paternal genomes suggests that methylation levels at repeat sequences are remarkably similar at the time of fertilisation or, as in the case of the L1 sequences, they become so during the first few cell cycles.
Current Opinion in Genetics & DevelopmentGerm cell specification in mice
301 Citations2009Mitinori Saitou
The recent clarification of the mechanism by which signaling activities confer the germ cell fate to the epiblast cells underscores the feasibility of generating the mammalian germ cell lineage in vitro.
Developmental DynamicsCell and molecular regulation of the mouse blastocyst
298 Citations2006Yojiro Yamanaka, Amy Ralston +2 more
Evidence that trophectoderm differentiation bears resemblance to the process of epithelialization and the importance of apical/basal protein complexes in regulating this process is described.
Journal of Biological ChemistrySall4 Interacts with Nanog and Co-occupies Nanog Genomic Sites in Embryonic Stem Cells
295 Citations2006Qiang Wu, Xi Chen +8 more
It is suggested that Sall4 and Nanog form a regulatory circuit similar to that of Oct4 and Sox2, which encode for key transcription factors in ES cells by cooperating with Nanog.
The Journal of Cell BiologyPericentric heterochromatin reprogramming by new histone variants during mouse spermiogenesis
291 Citations2007Jérôme Govin, Emmanuelle Escoffier +9 more
Investigations suggest that TH2B, an already identified testis-specific H2B variant of unknown function, could provide a platform for the structural transitions accompanying the incorporation of these new histone variants found in late spermiogenic cells.
Trends in GeneticsDNA demethylation by DNA repair
274 Citations2009Mary Gehring, Wolf Reik +1 more
What is known from flowering plants about the pathways and function of enzymatic dem methylation is examined and possible mechanisms whereby DNA repair might also underlie global demethylation in mammals are discussed.
Seminars in Cell and Developmental BiologyEpigenetic reprogramming in early mammalian development and following somatic nuclear transfer
267 Citations2003Wendy Dean, Fátima Santos +1 more
The concept of 'epigenetic checkpoints' for normal progression of development and the loss of totipotency is proposed and highlighted those areas with relevance to somatic nuclear cloning and the possibility of improving the efficiency of this process.
ScienceGerm Cell Specification in Mice
254 Citations2007Katsuhiko Hayashi, Susana M. Chuva de Sousa Lopes +1 more
Blim1 may have a role in the maintenance of early germ cell characteristics by ensuring their escape from the somatic fate as well as possible reversion to pluripotent stem cells.
Molecular and Cellular BiologySynergistic Function of DNA Methyltransferases Dnmt3a and Dnmt3b in the Methylation of <i>Oct4</i> and <i>Nanog</i>
245 Citations2007Jingyu Li, Mintie Pu +9 more
The results suggest that Dnmt3a and DnMT3b form a complex through direct contact in living cells and cooperate in the methylation of the promoters of Oct4 and Nanog during cell differentiation.
Genes & DevelopmentRole of Cdx2 and cell polarity in cell allocation and specification of trophectoderm and inner cell mass in the mouse embryo
244 Citations2008Agnieszka Jędrusik, David-Emlyn Parfitt +6 more
This work shows that outside cells become committed to the trophectoderm at the blastocyst stage through Cdx2 activity, but here it is shown that C dx2 can also act earlier to influence cell allocation, and describes a mutually reinforcing relationship between cellular polarity and Cdx1.
Cell stem cellSall4 Regulates Distinct Transcription Circuitries in Different Blastocyst-Derived Stem Cell Lineages
227 Citations2008Chin Yan Lim, Wai Leong Tam +10 more
It is demonstrated that a single transcription factor is able to regulate distinct core circuitries in two different blastocyst-derived stem cell lines, embryonic stem cells (ESCs) and extraembryonic endoderm (XEN) cells.
Mechanisms of DevelopmentStage- and cell-specific expression of Dnmt3a and Dnmt3b during embryogenesis
227 Citations2002Daisuke Watanabe, Isao Suetake +2 more
Genome ResearchGene Expression Profiling of Embryo-Derived Stem Cells Reveals Candidate Genes Associated With Pluripotency and Lineage Specificity
225 Citations2002Tetsuya S. Tanaka, Tilo Kunath +8 more
It is suggested that pluripotency requires a set of genes not expressed in other cell types, whereas lineage-restricted stem cells, like TS cells, express genes predictive of their differentiated lineage.
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