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Coordinated control of mRNA and rRNA processing regulates early mammalian embryogenesis [ChIP-Seq_PolII]

ABSTRACT: Stem cells are regulated by transcriptional networks controlling pluripotency and differentiation. How basic cellular processes like splicing or protein synthesis regulate stem cell function is less well understood. Here, we show that the RNA binding protein HTATSF1 controls protein synthesis by controlling several independent RNA processing steps during ribosome biogenesis. In a complex with ribosomal RNA transcription and processing factors, HTATSF1 regulates ribosomal RNA abundance. By binding to the U2snRNP complex, HTATSF1 also controls intron removal specifically in ribosomal protein transcripts. HTATSF1-mediated control of protein synthesis is essential for the transition from the naïve pre-implantation epiblast to the primed post-implantation epiblast, a stage of low protein synthesis levels, and during further differentiation towards neuroectoderm. Our results identify coordinated regulation of ribosomal RNA and protein biosynthesis by HTATSF1 as an essential mechanism to mediate protein synthesis control during early stages of mammalian embryogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE96594 | GEO | 2018/04/05

REPOSITORIES: GEO

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Coordinated control of mRNA and rRNA processing regulates early mammalian embryogenesis [ChIP-Seq_HTATSF1]

Project description:Stem cells are regulated by transcriptional networks controlling pluripotency and differentiation. How basic cellular processes like splicing or protein synthesis regulate stem cell function is less well understood. Here, we show that the RNA binding protein HTATSF1 controls protein synthesis by controlling several independent RNA processing steps during ribosome biogenesis. In a complex with ribosomal RNA transcription and processing factors, HTATSF1 regulates ribosomal RNA abundance. By binding to the U2snRNP complex, HTATSF1 also controls intron removal specifically in ribosomal protein transcripts. HTATSF1-mediated control of protein synthesis is essential for the transition from the naïve pre-implantation epiblast to the primed post-implantation epiblast, a stage of low protein synthesis levels, and during further differentiation towards neuroectoderm. Our results identify coordinated regulation of ribosomal RNA and protein biosynthesis by HTATSF1 as an essential mechanism to mediate protein synthesis control during early stages of mammalian embryogenesis.

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Coordinated control of mRNA and rRNA processing regulates early mammalian embryogenesis [RNA-Seq]

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De novo formation of apical-basal polarity by Rap1 regulates epiblast patterning

Project description:The epiblast is the first cell type that forms apical-basal polarity de novo as the mouse embryo implants into the maternal uterus, while the extraembryonic neighbours of the epiblast - trophectoderm and primitive endoderm - retain their pre-established polarity beyond implantation [1]; however, it is still unclear how the epiblast establishes apical-basal polarity de novo. Here, we focused on Rap1 signaling pathway, which is activated during the transition of the epiblast from the naïve to primed state of pluripotency during implantation [2]. Through the preestablished in vitro three-dimensional culture system [3], genetic knockouts and proximity-biotinylation analyses, we found that Rap1 integrates multiple signals that contribute to de novo formation of apical-basal polarity. Importantly, formation of apical-basal polarity in the epiblast is essential for its correct patterning and proper communication with the extraembryonic lineages. Altogether, these results not only dissect molecular details of de novo apical-basal polarity formation, but also have broader implications for epithelial polarity and development.

2022-06-14 | PXD028315 | Pride

Reconstituting the transcriptome and DNA methylome landscapes of human implantation at single-cell resolution

Project description:Implantation is a milestone event during mammalian embryogenesis. Due to the extreme difficulty of obtaining in vivo human early post-implantation embryos, the gene regulatory network and epigenetics controlling human embryo implantation remains elusive. Here, combining an in vitro culture system for human post-implantation development and single-cell omics sequencing technologies, over 10,000 single cells at five representative stages of pre/post-implantation development were systematically analyzed. Unsupervised dimensionality reduction and clustering algorithm of the transcriptome data show stepwise implantation routes for the epiblast, primitive endoderm, and trophectoderm lineages, suggesting preparation for the establishment of a mother-to-offspring connection after implantation. Female embryos showed asynchronous progress of dosage loss of X chromosomes during implantation. Furthermore, using the single cell trio-Seq (scTrio-Seq) strategy, re-methylation of the genomes of all the three lineages was unambiguously revealed. Surprisingly, the genome re-methylation of PE lineage were much slower than both EPI and TE lineages during the implantation process, indicating distinct methylome features between EPI and PE although both of which were derived from ICM. Collectively, our work paves the way for understanding the complex molecular mechanisms that regulate human embryo implantation, informing new insights and future efforts in early embryonic development and reproductive medicine.

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Novel cell lines from mouse epiblast share defining features with human embryonic stem cells

Project description:The application of human embryonic stem (ES) cells has an inherent reliance on understanding the starting cell population. Human ES cells differ from mouse ES cells and the specific embryonic origin of both cell types is unclear. Previous work suggested that mouse ES cells could only be obtained from the embryo prior to implantation in the uterus. Here we show that cell lines can be derived from the epiblast, a tissue of the post-implantation embryo that generates the embryo proper. These cells, which we refer to as EpiSCs (post-implantation epiblast-derived stem cells), express transcription factors known to regulate pluripotency, maintain their genomic integrity, and robustly differentiate into the major somatic cell types as well as primordial germ cells (PGCs). The post-ES cell lines are distinct from mouse ES cells in their epigenetic state and the signals controlling their differentiation. Furthermore, post-ES and human ES cells share patterns of gene expression and signalling responses that normally function in the epiblast. These results show that epiblast cells can be maintained as stable cell lines and interrogated to understand how pluripotent cells generate distinct fates during early development. This SuperSeries is composed of the SubSeries listed below.

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Epiblast inducers capture mouse Trophectoderm Stem Cells in vitro and pattern blastoids for implantation in utero. [scRNAseq]

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Transcription profiling of mouse ES cells and EpiSCs

Project description:The application of human embryonic stem (ES) cells in medicine; and biology has an inherent reliance on understanding the starting; cell population. Human ES cells differ from mouse ES cells and the; specific embryonic origin of both cell types is unclear. Previous; work suggested that mouse ES cells could only be obtained from; the embryo before implantation in the uterus1â5. Here we show; that cell lines can be derived from the epiblast, a tissue of the postimplantation; embryo that generates the embryo proper. These; cells, which we refer to as EpiSCs (post-implantation epiblastderived; ES cells), express transcription factors known to regulate; pluripotency, maintain their genomic integrity, and robustly differentiate; into the major somatic cell types as well as primordial; germ cells. The EpiSC lines are distinct from mouse ES cells in; their epigenetic state and the signals controlling their differentiation. Furthermore, EpiSC and human ES cells share patterns of; gene expression and signalling responses that normally function; in the epiblast. These results show that epiblast cells can be maintained; as stable cell lines and interrogated to understand how; pluripotent cells generate distinct fates during early development. *Note: EpiSCs were previously referred to as post-ES cells Experiment Overall Design: 3 biological replicates of each cell type (EpiSC and mouse ES) were compared.

2008-06-19 | E-GEOD-7866 | biostudies-arrayexpress

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