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Naïve human embryonic stem cells can give rise to cells with trophoblast-like transcriptome and methylome

ABSTRACT: Naïve human embryonic stem cells can give rise to cells with trophoblast-like transcriptome and methylome

PROVIDER: PRJNA638347 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11742234_1.fastq.gz	Fastqsanger.gz
	SRR11742234_2.fastq.gz	Fastqsanger.gz
	SRR11742235_1.fastq.gz	Fastqsanger.gz
	SRR11742235_2.fastq.gz	Fastqsanger.gz
	SRR11742236_1.fastq.gz	Fastqsanger.gz

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Naïve human embryonic stem cells can give rise to cells with trophoblast-like transcriptome and methylome [Bisulfite-Seq]

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Project description:Human embryonic stem cells (hESCs) readily differentiate to somatic or germ lineages but have impaired ability to form extra-embryonic lineages such as placenta or yolk sac. Here we demonstrate that hESCs cultured in naïve media conditions can be converted into cells that exhibit the cellular and molecular phenotypes of human trophoblast stem cells (hTSCs) derived from human placenta or blastocyst. The resulting “transdifferentiated” hTSCs show reactivation of core placental genes, acquisition of a placenta-like methylome, and the ability to differentiate to extravillous trophoblasts and syncytiotrophoblasts. Modest differences are observed between transdifferentiated and placental hTSCs, most notably in the expression of certain imprinted loci. These results indicate that naïve hESCs can differentiate to extra-embryonic lineage, and demonstrate a new way of modeling human trophoblast specification and placental methylome establishment.

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Project description:Naïve human pluripotent stem cells (hPSCs) provide a unique experimental platform of cell fate decisions during pre-implantation development, but their lineage potential remains incompletely characterized. As naïve hPSCs share transcriptional and epigenomic signatures with trophoblast cells, it has been proposed that the naïve state may have enhanced predisposition for differentiation along this extraembryonic lineage. Here we examined the trophoblast potential of isogenic naïve and primed hPSCs. We found that naïve hPSCs can directly give rise to human trophoblast stem cells (hTSCs) and undergo further differentiation into both extravillous and syncytiotrophoblast. In contrast, primed hPSCs do not support hTSC derivation, but give rise to non-self-renewing cytotrophoblasts in response to BMP4. Global transcriptome and chromatin accessibility analyses indicate that hTSCs derived from naïve hPSCs acquire features of pre-implantation trophectoderm. The derivation of hTSCs from naïve hPSCs will enable elucidation of early mechanisms that govern normal human trophoblast development and associated pathologies.

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