The timing mechanism for the first lineage specification in the mouse embryo
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PROVIDER: PRJNA513332 | ENA |
REPOSITORIES: ENA
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Project description:The transition from totipotency to pluripotency and subsequent differentiation in the mammalian embryo segregates embryonic and extra-embryonic progenitor cells. Despite its central importance, it remains entirely unknown how the timing of this major process is regulated. Here, we uncover that Tfap2c and Tead4 mediated transcriptional activity work in concert with the Rho GTPase mediated activation of actomyosin at the 8-cell stage as the upstream factors that trigger cell polarization and hence the first cell fate segregation in the mouse embryo. We show that they act together to control the establishment of cell polarisation, the activation of polarity dependent Hippo signalling, and the early expression of transcription factors required for the differentiation of the first extra-embryonic lineage. These results define the key step in the transition from totipotency to pluripotency and its relationship to the first cell fate specification event in the mouse embryo.
2019-12-30 | GSE124755 | GEO
Project description:During postimplantation development of the mouse embryo, descendants of the inner cell mass cells in the early epiblast transit from the naïve pluripotent state to the primed pluripotent state. Concurrent with the transition of the pluripotency states is the specification of cell lineages and formation of germ layers in the embryos that serves as the blueprint for embryogenesis. Fate mapping and lineage analysis studies have revealed that cells in different regions of the germ layers acquire location-specific cell fates during gastrulation. The regionalization of cell fates heralding the formation of the basic body plan is conserved in vertebrate embryos at a common phylotypic stage of development. Knowledge of the molecular regulation that underpin the lineage specification and tissue patterning is instrumental for understanding embryonic programming and stem cell-based translational study. However, a genome-wide molecular annotation of lineage segregation and tissue architecture of post-implantation embryo has yet to be undertaken. Here, we reported a spatially resolved transcriptome of cell populations at defined positions in the germ layers over the period of pre- to late gastrulation development. This spatio-temporal transcriptome provides high resolution digitized gene expression profiles and defines the molecular attribute of the genealogy of lineages and continuum of pluripotency states in time and space. The transcriptome further identifies the networks of molecular determinants that drive lineage specification and tissue patterning in the early postimplantation mouse embryo.
2019-08-08 | GSE120963 | GEO
Project description:Stickleback genome-wide replication timing from whole embryo
| PRJNA497600 | ENA
Project description:Differentiation of mouse embryonic stem cells (mESCs) is accompanied by global changes in replication timing. To elucidate this reorganization process and explore its potential impact on mouse development, we constructed genome-wide replication-timing profiles of 15 independent mouse cell types representing nine different stages of early mouse development, including all three germ layers. Overall, 45% of the genome exhibits significant changes in replication timing between cell types, indicating that replication-timing regulation is more extensive than previously estimated from neural differentiation. Intriguingly, analysis of early and late epiblast cell culture models suggest that the earliest changes in development include extensive lineage-independent early-to-late replication switches that are completed at a stage equivalent to the post-implantation epiblast, prior to germ layer specification and down-regulation of key pluripotency transcription factors (Oct4/Nanog/Sox2). These changes were stable in all subsequent lineages and involved a class of irreversibly silenced genes that were re-positioned closer to the nuclear periphery. Lineage-specific, late-to-early and early-to-late replication switches followed, which created cell-type specific replication profiles. Importantly, partially reprogrammed induced pluripotent stem cells (piPSCs) failed to restore ESC-specific replication timing and transcription programs particularly within regions of lineage-independent early-to-late replication changes, as well as the inactive X-chromosome. We conclude that lineage-independent, early-to-late replication-timing switches that occur in the post-implantation epiblast embody an epigenetic commitment to differentiation prior to germ layer specification. 22 cell lines, with a total of 36 individual replicates (i.e. 14 in duplicates, 8 in single replicates)
2010-05-19 | E-GEOD-17983 | biostudies-arrayexpress
Project description:Molecular architecture of lineage specification and tissue organization in early mouse embryo
| PRJNA495153 | ENA
Project description:Lineage specification and X chromosome dosage compensation are two crucial biological processes that occur during preimplantation embryonic development. While these processes have been studied extensively in mice and humans, they are less understood in other species. This study aims to provide fundamental insights into bovine preimplantation development using single-cell RNA-sequencing. The study analyzes the transcriptomes of 286 individual cells and reveals that bovine trophectoderm/inner cell mass transcriptomes diverge at the early blastocyst stage, after cavitation but before blastocyst expansion. The study also identifies transcriptomic markers and provides the timing of lineage specification events in the bovine embryo. Moreover, the study confirms the occurrence of X chromosome dosage compensation from morula to middle blastocyst and reveals that this compensation results from downregulation of X-linked genes in female embryonic cells. The transcriptional atlas generated by this study is expected to be widely useful in improving our understanding of mammalian early embryo development.
2024-02-20 | GSE239782 | GEO
Project description:Single Embryo Repli-Seq was utilized to investigate the replication timing in zygotes and 2-cell cleavage stage embryos. The aim was to understand the temporal progression of DNA replication during the early stages of embryonic development in mammals.
2024-05-23 | GSE237400 | GEO
Project description:In the preimplantation mouse embryo TEAD4 is critical to establishing the trophectoderm (TE)-specific transcriptional program and segregating TE from the inner cell mass (ICM). However, TEAD4 is expressed both in the TE and the ICM. Thus, differential function of TEAD4 rather than expression itself regulates specification of the first two cell lineages. We used ChIP-seq to define genome-wide TEAD4 target genes and asked how transcription of TEAD4 target genes is specifically maintained in the TE. Our analyses revealed an evolutionarily conserved mechanism, in which lack of nuclear localization of TEAD4 impairs the TE-specific transcriptional program in inner blastomeres, thereby allowing their maturation towards the ICM lineage. Restoration of TEAD4 nuclear localization maintains the TE-specific transcriptional program in the inner blastomeres and prevents segregation of the TE and ICM lineages and blastocyst formation. We propose that altered subcellular localization of TEAD4 in blastomeres dictates first mammalian cell fate specification. ChIPseq profiles of TEAD4, IgG, Input in Mouse trophoblast stem cells using Illumina HiSeq 2000 and Illumina Genome Analyzer IIx
2012-04-18 | E-GEOD-37350 | biostudies-arrayexpress
Project description:Differentiation of mouse embryonic stem cells (mESCs) is accompanied by global changes in replication timing. To elucidate this reorganization process and explore its potential impact on mouse development, we constructed genome-wide replication-timing profiles of 15 independent mouse cell types representing nine different stages of early mouse development, including all three germ layers. Overall, 45% of the genome exhibits significant changes in replication timing between cell types, indicating that replication-timing regulation is more extensive than previously estimated from neural differentiation. Intriguingly, analysis of early and late epiblast cell culture models suggest that the earliest changes in development include extensive lineage-independent early-to-late replication switches that are completed at a stage equivalent to the post-implantation epiblast, prior to germ layer specification and down-regulation of key pluripotency transcription factors (Oct4/Nanog/Sox2). These changes were stable in all subsequent lineages and involved a class of irreversibly silenced genes that were re-positioned closer to the nuclear periphery. Lineage-specific, late-to-early and early-to-late replication switches followed, which created cell-type specific replication profiles. Importantly, partially reprogrammed induced pluripotent stem cells (piPSCs) failed to restore ESC-specific replication timing and transcription programs particularly within regions of lineage-independent early-to-late replication changes, as well as the inactive X-chromosome. We conclude that lineage-independent, early-to-late replication-timing switches that occur in the post-implantation epiblast embody an epigenetic commitment to differentiation prior to germ layer specification.
2009-11-25 | GSE17983 | GEO
Project description:In the preimplantation mouse embryo TEAD4 is critical to establishing the trophectoderm (TE)-specific transcriptional program and segregating TE from the inner cell mass (ICM). However, TEAD4 is expressed both in the TE and the ICM. Thus, differential function of TEAD4 rather than expression itself regulates specification of the first two cell lineages. We used ChIP-seq to define genome-wide TEAD4 target genes and asked how transcription of TEAD4 target genes is specifically maintained in the TE. Our analyses revealed an evolutionarily conserved mechanism, in which lack of nuclear localization of TEAD4 impairs the TE-specific transcriptional program in inner blastomeres, thereby allowing their maturation towards the ICM lineage. Restoration of TEAD4 nuclear localization maintains the TE-specific transcriptional program in the inner blastomeres and prevents segregation of the TE and ICM lineages and blastocyst formation. We propose that altered subcellular localization of TEAD4 in blastomeres dictates first mammalian cell fate specification.
2012-04-18 | GSE37350 | GEO