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Capture of mouse and human stem cells with features of formative pluripotency

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE131556 | GEO | 2020/12/04

REPOSITORIES: GEO

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Capture of mouse and human stem cells with features of formative pluripotency

Project description:Pluripotent cells emerge as a naïve founder population in the blastocyst, acquire capacity for germline and soma formation, and then undergo lineage priming. Mouse embryonic stem (ES) cells and epiblast stem cells (EpiSCs) respectively represent the initial naïve and final primed phases of pluripotency. Here we investigated the intermediate formative stage. Using minimal exposure to specification cues, we derived stem cells from formative mouse epiblast. Unlike ES cells or EpiSCs, formative stem (FS) cells responded directly to germ cell induction. They colonised somatic tissues and germline in chimaeras. Whole transcriptome analyses showed similarity to pre-gastrulation formative epiblast. Signal responsiveness and chromatin accessibility features reflect lineage capacitation. Furthermore, FS cells showed distinct transcription factor dependencies, relying critically on Otx2. Finally, FS cell culture conditions applied to human naïve cells or embryos supported expansion of similar stem cells, consistent with a conserved staging post on the trajectory of mammalian pluripotency. This SuperSeries is composed of the SubSeries listed below.

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Project description:Pluripotent cells emerge as a naive founder population in the blastocyst, acquire capacity for germline and soma formation, and then undergo lineage priming. Mouse embryonic stem cells (ESCs) and epiblast-derived stem cells (EpiSCs) represent the initial naive and final primed phases of pluripotency, respectively. Here, we investigate the intermediate formative stage. Using minimal exposure to specification cues, we derive stem cells from formative mouse epiblast. Unlike ESCs or EpiSCs, formative stem (FS) cells respond directly to germ cell induction. They colonize somatic tissues and germline in chimeras. Whole-transcriptome analyses show similarity to pre-gastrulation formative epiblast. Signal responsiveness and chromatin accessibility features reflect lineage capacitation. Furthermore, FS cells show distinct transcription factor dependencies, relying critically on Otx2. Finally, FS cell culture conditions applied to human naive cells or embryos support expansion of similar stem cells, consistent with a conserved staging post on the trajectory of mammalian pluripotency.

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Project description:Pluripotent cells emerge as a naïve founder population in the blastocyst, acquire capacity for germline and soma formation, and then undergo lineage priming. Mouse embryonic stem (ES) cells and epiblast stem cells (EpiSCs) respectively represent the initial naïve and final primed phases of pluripotency. Here we investigated the intermediate formative stage. Using minimal exposure to specification cues, we derived stem cells from formative mouse epiblast. Unlike ES cells or EpiSCs, formative stem (FS) cells responded directly to germ cell induction. They colonised somatic tissues and germline in chimaeras. Whole transcriptome analyses showed similarity to pre-gastrulation formative epiblast. Signal responsiveness and chromatin accessibility features reflect lineage capacitation. Furthermore, FS cells showed distinct transcription factor dependencies, relying critically on Otx2. Finally, FS cell culture conditions applied to human naïve cells or embryos supported expansion of similar stem cells, consistent with a conserved staging post on the trajectory of mammalian pluripotency.

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Capture of mouse and human stem cells with features of formative pluripotency [mouse, RNA-Seq 1]

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