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PRC2 shields naive pluripotent cells from trophectoderm and mesoderm differentiation.

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE181244 | GEO | 2021/08/23

REPOSITORIES: GEO

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PRC2 shields naive pluripotent cells from trophectoderm and mesoderm differentiation [ChIP-seq]

Project description:The first lineage choice made in human embryo development separates trophectoderm from the inner cell mass, which proceeds to form the pluripotent epiblast and primitive endoderm. Trophectoderm on the other hand gives rise to the placenta. Naïve pluripotent stem cells are derived from the pluripotent epiblast of the blastocyst and offer possibilities to explore how lineage integrity is maintained. Here, we discover that Polycomb repressive complex 2 (PRC2) restricts an intrinsic capacity of naïve pluripotent stem cells to give rise to trophectoderm. Through quantitative epigenome profiling, we find that broad histone H3 lysine 27 trimethylation (H3K27me3) hypermethylation is a common feature of naïve pluripotency across species. We define a previously unappreciated, naïve-specific set of bivalent promoters, featuring PRC2-mediated H3K27me3 concomitant with H3K4me3. Naïve bivalency maintains key trophectoderm transcription factors in a transcriptionally poised state that is resolved to an active state upon depletion of H3K27me3 via inhibition of the enzymatic subunits of PRC2, EZH1/2. Conversely, primed human embryonic stem cells cannot be driven towards trophectoderm development via PRC2 inhibition. While naïve and primed hESCs share the majority of bivalent promoters, PRC2 contributes to the repression of largely non-overlapping subsets of these promoters in each state, hence H3K27me3-mediated repression provides a highly adaptive mechanism to restrict lineage potential during early human development.

2021-08-23 | GSE181241 | GEO

PRC2 shields naive pluripotent cells from trophectoderm and mesoderm differentiation [RNA-seq]

2021-08-23 | GSE181242 | GEO

Polycomb repressive complex 2 shields naive human pluripotent cells from trophectoderm differentiation.

Project description:The first lineage choice in human embryo development separates trophectoderm from the inner cell mass. Naïve human embryonic stem cells are derived from the inner cell mass and offer possibilities to explore how lineage integrity is maintained. Here, we discover that polycomb repressive complex 2 (PRC2) maintains naïve pluripotency and restricts differentiation to trophectoderm and mesoderm lineages. Through quantitative epigenome profiling, we found that a broad gain of histone H3 lysine 27 trimethylation (H3K27me3) is a distinct feature of naïve pluripotency. We define shared and naïve-specific bivalent promoters featuring PRC2-mediated H3K27me3 concomitant with H3K4me3. Naïve bivalency maintains key trophectoderm and mesoderm transcription factors in a transcriptionally poised state. Inhibition of PRC2 forces naïve human embryonic stem cells into an 'activated' state, characterized by co-expression of pluripotency and lineage-specific transcription factors, followed by differentiation into either trophectoderm or mesoderm lineages. In summary, PRC2-mediated repression provides a highly adaptive mechanism to restrict lineage potential during early human development.

| S-EPMC9203276 | biostudies-literature

PRC2 shields naive pluripotent cells from trophectoderm and mesoderm differentiation.

Project description:PRC2 shields naive pluripotent cells from trophectoderm and mesoderm differentiation.

| PRJNA751099 | ENA

PRC2 shields naïve human pluripotent cells from trophectoderm and mesoderm differentiation [scRNA-seq]

Project description:Single-cell RNA-seq reveals that Polycomb repressive complex 2 (PRC2) maintains naïve pluripotency and restricts an intrinsic capacity of pre-implantation pluripotent stem cells to give rise to trophectoderm and mesoderm lineages. Inhibition of PRC2 forces naïve hESC into an ‘activated’ state through which differentiation into either trophectoderm or mesoderm lineages is triggered. This trajectory is distinct from embryonic lineage specification out of the post-implantation pluripotent state, hence PRC2-mediated repression provides a highly adaptive mechanism to restrict lineage potential during early human development.

2022-03-14 | GSE196280 | GEO

PRC2 shields naive pluripotent cells from trophectoderm and mesoderm differentiation [RNA-seq]

Project description:PRC2 shields naive pluripotent cells from trophectoderm and mesoderm differentiation [RNA-seq]

| PRJNA751101 | ENA

PRC2 shields naive pluripotent cells from trophectoderm and mesoderm differentiation [ChIP-seq]

Project description:PRC2 shields naive pluripotent cells from trophectoderm and mesoderm differentiation [ChIP-seq]

| PRJNA751100 | ENA

Modeling human extraembryonic mesoderm cells using naive pluripotent stem cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-08-01 | GSE191286 | GEO

PRC2 shields naïve human pluripotent cells from trophectoderm and mesoderm differentiation [scRNA-seq]

Project description:PRC2 shields naïve human pluripotent cells from trophectoderm and mesoderm differentiation [scRNA-seq]