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

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE182791 | GEO | 2022/05/16

REPOSITORIES: GEO

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Derivation of trophoblast stem cells from naïve human pluripotent stem cells

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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 are similar to blastocyst-derived hTSCs and acquire features of post-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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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.

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Protocol to derive human trophoblast stem cells directly from primed pluripotent stem cells.

Project description:Human trophoblast stem cells (hTSCs) are useful for studying human placenta development and diseases, but primed human pluripotent stem cells (hPSCs) routinely cultured in most laboratories do not support hTSC derivation. Here, we present a protocol to derive hTSCs directly from primed hPSCs. This approach, containing two strategies either with or without bone morphogenetic protein 4 (BMP4), provides a simple and accessible tool for deriving hTSCs to study placenta development and disease modeling without ethical limitations or reprogramming process. For complete details on the use and execution of this protocol, please refer to Wei et al. (2021).

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

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

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