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Induction of human trophoblast stem-like cells from primed pluripotent stem cells

ABSTRACT: Induction of human trophoblast stem-like cells from primed pluripotent stem cells

PROVIDER: PRJNA737492 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14808600_1.fastq.gz	Fastqsanger.gz
	SRR14808600_2.fastq.gz	Fastqsanger.gz
	SRR14808601_1.fastq.gz	Fastqsanger.gz
	SRR14808601_2.fastq.gz	Fastqsanger.gz
	SRR14808580_1.fastq.gz	Fastqsanger.gz

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Induction of human trophoblast stem-like cells from primed pluripotent stem cells

Project description:The placenta is a transient but important multifunctional organ crucial for healthy pregnancy for both mother and fetus. Nevertheless, limited access to human placenta samples and the paucity of a proper in vitro model system has hampered our understanding of the mechanisms underlying early human placental development and placenta-associated pregnancy complications. To overcome these constraints, we established a simple procedure with a short-term treatment of bone morphogenetic protein 4 (BMP4) in trophoblast stem cell culture medium (TSCM) to convert human primed pluripotent stem cells (PSCs) to trophoblast stem-like cells (TSLCs). These TSLCs show not only comparable morphology and gene expression profile to bona fide human trophoblast stem cells (TSCs) but also long-term self-renewal capacity with bipotency that allows the cells to differentiate into extravillous trophoblasts (EVT) and syncytiotrophoblasts (ST). These indicate that TSLCs are equivalent to genuine human TSCs. Our data suggest a straightforward approach to make human TSCs directly from pre-existing primed PSCs and provide a valuable opportunity to study human placenta development and pathology even from patients with placenta-related diseases.

2021-12-31 | GSE178162 | GEO

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

Induction of trophoblast stem cells from human pluripotent stem cells

Project description:Induction of trophoblast stem cells from human pluripotent stem cells

| PRJNA559732 | 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

Derivation of functional trophoblast stem cells from human primed pluripotent stem cells

Project description:Derivation of functional trophoblast stem cells from human primed pluripotent stem cells

| PRJNA757782 | ENA

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

2022-05-06 | PXD028162 | Pride

Induction of trophoblast stem cells from human pluripotent stem cells [ATAC-seq]

Project description:Induction of trophoblast stem cells from human pluripotent stem cells [ATAC-seq]

| PRJNA559737 | ENA

Induction of trophoblast stem cells from human pluripotent stem cells [RNA-seq]

Project description:Induction of trophoblast stem cells from human pluripotent stem cells [RNA-seq]

| PRJNA559736 | ENA

Induction of trophoblast stem cells from human pluripotent stem cells [ChIP-seq]

Project description:Induction of trophoblast stem cells from human pluripotent stem cells [ChIP-seq]

| PRJNA559735 | ENA

Derivation of functional trophoblast stem cells from human primed pluripotent stem cells [scRNA-seq]

Project description:Trophoblast stem cells (TSC) have recently been derived from human embryos, and early first trimester placenta; however, aside from ethical challenges, the unknown disease potential of these cells limits their scientific utility. We have previously established a BMP4-based two-step protocol for differentiation of primed human pluripotent stem cells (hPSC) into functional trophoblast; however, those trophoblast could not be maintained in a self-renewing TSC-like state. Here, we use the first step from this protocol, followed by a switch to a newly-developed TSC media, to derive bona-fide TSC. We show that these cells resemble placenta- and naïve hPSC-derived TSC, based on their transcriptome, as well as in vitro and in vivo differentiation potential. We conclude that primed hPSC can be used to generate functional TSC, through a simple protocol which can be applied to a widely-available set of existing hPSC, including induced pluripotent stem cells derived from patients with known birth outcomes.

2022-05-16 | GSE182790 | GEO

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