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Mus musculus

ABSTRACT: Breaking the lineage barrier: Direct induction of trophoblast stem cells from murine fibroblasts

PROVIDER: PRJNA270765 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR1724080_1.fastq.gz	Fastqsanger.gz
	SRR1724080_2.fastq.gz	Fastqsanger.gz
	SRR1724081_1.fastq.gz	Fastqsanger.gz
	SRR1724081_2.fastq.gz	Fastqsanger.gz
	SRR1724082_1.fastq.gz	Fastqsanger.gz

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Mus musculus

Project description:Breaking the first lineage barrier: Direct induction of trophoblast stem cells from murine fibroblasts

| PRJNA270252 | ENA

Integrated Multi-Omics Reveal Polycomb Repressive Complex 2 Restricts Human Trophoblast Induction

Project description:Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought to lack chromatin-based lineage barriers. However, this assumption has not been tested. Here, we define the chromatin-associated proteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Our integrated analysis reveals differences in the relative abundance and activities of distinct chromatin modules. We identify a strong enrichment of Polycomb Repressive Complex 2 (PRC2)-associated H3K27me3 in naive pluripotent stem cell chromatin, and H3K27me3 enrichment at promoters of lineage-determining genes, including trophoblast regulators. PRC2 activity acts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, while inhibition of PRC2 promotes trophoblast fate induction and cavity formation in human blastoids. Together, our results establish that human naive pluripotent stem cells are not epigenetically unrestricted, but instead possess chromatin mechanisms that oppose the induction of alternative cell fates.

2022-05-09 | PXD032792 | Pride

Polycomb Repressive Complex 2 Restricts Human Naive Pluripotent Stem Cell to Trophoblast Fate Induction

Project description:Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought to lack chromatin-based lineage barriers. However, this assumption has not been tested. Here, we apply multi-omics to comprehensively define the chromatin-associated proteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Integrating the chromatin-bound proteome and histone modification data sets reveals differences in the relative abundance and activities of distinct chromatin modules, identifying a strong enrichment of Polycomb Repressive Complex 2 (PRC2)-associated H3K27me3 in naive pluripotent stem cell chromatin. Single-cell approaches and human blastoid models reveal that PRC2 activity acts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, and inhibiting PRC2 promotes trophoblast fate induction and cavity formation. Our results establish that human naive pluripotent stem cells are not epigenetically unrestricted, but instead possess chromatin mechanisms that oppose the induction of alternative cell fates.

2022-05-06 | PXD028111 | Pride

Direct Induction of Trophoblast Stem Cells from Human Fibroblasts

Project description:Direct Induction of Trophoblast Stem Cells from Human Fibroblasts

| PRJNA562835 | ENA

Direct Induction of Trophoblast Stem Cells from Human Fibroblasts

Project description:Direct Induction of Trophoblast Stem Cells from Human Fibroblasts

| PRJNA916261 | ENA

Integrated Multi-Omics Reveal Polycomb Repressive Complex 2 Restricts Human Trophoblast Induction

Project description:Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought to lack chromatin-based lineage barriers. However, this assumption has not been tested. Here, we apply multi-omics to comprehensively define the chromatin-associated proteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Integrating the chromatin-bound proteome and histone modification data sets reveals differences in the relative abundance and activities of distinct chromatin modules, identifying a strong enrichment of Polycomb Repressive Complex 2 (PRC2)-associated H3K27me3 in naive pluripotent stem cell chromatin. Single-cell approaches and human blastoid models reveal that PRC2 activity acts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, and inhibiting PRC2 promotes trophoblast fate induction and cavity formation. Our results establish that human naive pluripotent stem cells are not epigenetically unrestricted, but instead possess chromatin mechanisms that oppose the induction of alternative cell fates. Data originating from the LC-MS/MS analysis of the histone PTMs can be consulted via this project.

2022-05-06 | PXD028162 | Pride

Direct Induction of Trophoblast Stem Cells from Human Fibroblasts (RRBS)

Project description:Direct Induction of Trophoblast Stem Cells from Human Fibroblasts (RRBS)

| PRJNA562841 | ENA

Direct Induction of Trophoblast Stem Cells from Human Fibroblasts (RNA-seq)

Project description:Direct Induction of Trophoblast Stem Cells from Human Fibroblasts (RNA-seq)

| PRJNA562840 | ENA

Breaking the first lineage barrier: Direct induction of trophoblast stem cells from murine fibroblasts

Project description:Trophoblast stem cells represent the stem cell population of the extra-embryonic lineage and arise as a result of the first cell fate decision. From blastocyst stage onwards, a distinct epigenetic lineage barrier strictly separates mouse embryonic and extra-embryonic lineages. Recently, it has been shown that this epigenetic barrier cannot be fully overcome as the expression of TS-determining factors in embryonic stem cells lead to incomplete transdifferentiation. Here, we demonstrate that transient expression of Tfap2c, Gata3, Eomes and Ets2 in fibroblasts suffices to generate cells which are almost identical to trophoblast stem cells based on morphology, expression and methylation pattern. Further, these induced trophoblast stem cells display transgene independent self-renewal, differentiate along the extra-embryonic lineage and chimerize the placenta upon blastocyst injection. Our findings provide insights into the transcription factor networks governing trophoblast stem cell identity and offer a new tool for studying the hierarchy of those factors.

2015-10-01 | GSE64145 | GEO

Breaking the lineage barrier: Direct induction of trophoblast stem cells from murine fibroblasts

Project description:Trophoblast stem cells represent the stem cell population of the extraembryonic lineage and arise as result of the first cell fate decision. From the blastocyst stage onwards, the extraembryonic lineage is strictly separated from the embryonic lineage by a distinct epigenetic lineage barrier. Recently, it has been shown, that this epigenetic barrier cannot be fully overcome as the expression of TS-determining factors in embryonic stem cells lead to incomplete trans-differentiation. Here we demonstrate that transient expression of Tfap2c, Gata3, Eomes and Ets2 in fibroblasts suffices to generate cells, which are almost equivalent to trophoblast stem cells based on morphology, expression and methylation patterns. Further, these induced trophoblast stem cells display self-renewal without exogenous factor expression, differentiate along the extraembryonic lineage and chimerize the placenta upon blastocyst injection. Our findings provide insights into transcription factor networks governing TSC identity and offer a new tool for studying the hierarchy of those factors.

2015-10-01 | GSE64339 | GEO

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