Nave 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 nave hPSCs share transcriptional and epigenomic signatures with trophoblast cells, it has been proposed that the nave state may have enhanced predisposition for differentiation along this extraembryonic lineage. Here we examined the trophoblast potential of isogenic nave and primed hPSCs. We found that nave 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 nave hPSCs acquire features of pre-implantation trophectoderm. The derivation of hTSCs from nave hPSCs will enable elucidation of early mechanisms that govern normal human trophoblast development and associated pathologies. SOURCE: Bo Zhang (bzhang29@wustl.edu) - Zhang Washington University School of Medicine

Pluto Bioinformatics

GSE138688: Derivation of trophoblast stem cells from nave human pluripotent stem cells [RNA-seq]