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NOTUM-MEDIATED WNT SILENCING DRIVES EXTRAVILLOUS TROPHOBLAST CELL LINEAGE DEVELOPMENT [CHIR99021]

ABSTRACT: NOTUM-MEDIATED WNT SILENCING DRIVES EXTRAVILLOUS TROPHOBLAST CELL LINEAGE DEVELOPMENT [CHIR99021]

PROVIDER: PRJNA848827 | ENA |

REPOSITORIES: ENA

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NOTUM-MEDIATED WNT SILENCING DRIVES EXTRAVILLOUS TROPHOBLAST CELL LINEAGE DEVELOPMENT [CHIR99021]

Project description:WNT activated signal transduction is a conserved regulator of morphogenesis of many organ systems, including the placenta. In human trophoblast stem (TS) cells, activation of canonical WNT signaling is a key to maintenance of the TS cell stem state. NOTUM, a negative regulator of canonical WNT signaling, was prominently expressed in first trimester EVT cells developing in situ and upregulated in EVT cells derived from human TS cells. Furthermore, NOTUM was required for human TS cell differentiation to EVT cells. Canonical WNT signaling is essential for maintaining human trophoblast cell stemness and prevention of human TS cell differentiation. Downregulation of canonical WNT signaling via the actions of NOTUM is required for EVT cell differentiation.

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NOTUM-MEDIATED WNT SILENCING DRIVES EXTRAVILLOUS TROPHOBLAST CELL LINEAGE DEVELOPMENT

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Wnt signaling activation confers a syncytiotrophoblast progenitor state on trophoblast stem cells of cynomolgus monkey.

Project description:Trophoblast stem cells (TSCs), derived from the trophectoderm of the blastocyst, are used as an in vitro model to reveal the underlying mechanisms of placentation in the mammal. In humans, suitable culture conditions for TSC derivation have been recently discovered. The established human TSCs differentiate efficiently toward two trophoblast subtypes, i.e., syncytiotrophoblast (STB) and extravillous trophoblast. On the other hand, the differentiation efficiencies were lower in macaque TSCs compared to human TSCs. Here, we demonstrate that the activation of Wnt signaling induced trophoblastic lineage switching to STB progenitor state. macTSCs highly expressed STB progenitor markers and obtained forskolin responsiveness by CHIR99021 treatment.

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RRBS investigation of matched side-population trophoblast, cytotrophoblast and extravillous trophoblast populations from 4 human placentae

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Human uterine Natural Killer cells regulate differentiation of extravillous trophoblast early in pregnancy - scRNA-seq data

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