Human primed and naïve PSCs are both competent in differentiating into bona fide trophoblast stem cells

Abstract

SummaryCells of the trophoblast lineage constitute the major part of placental tissues in higher mammals. Recent derivation of human trophoblast stem cells (TSC) from placental cytotrophoblasts (CT) and from human naïve PSCs opens new opportunities for studying development and function of human placenta. Several recent reports have suggested that naïve human PSCs retain an exclusive potential to give rise to bona fide TSCs. Here we report that inhibition of TGFβ pathway and avoiding WNT stimulation, leads to direct and robust conversion of primed human pluripotent stem cells into TSCs. Systematic side by side comparative analysis showed that the latter are equivalent to previously derived TSC lines. Primed PSC derived TSC lines exhibit self-renewal, are able to differentiate into the main trophoblast lineages, and present RNA and epigenetic profiles that are indistinguishable from the TSC lines derived from placenta or naïve PSCs. Our findings underscore a residual plasticity in primed human PSCs that allows converting directly into pre-implantation extra-embryonic cell lineages.HighlightsPrimed human PSCs readily convert into TSCs upon inhibition of TGF pathwayCHIR inhibits conversion to TSC in primed but not in naive hPSCsPrimed human PSC derived TSCs line are indistinguishable from placental and naïve derived TSCsYAP is sufficient for TSC induction from hPSCs and necessary for TSC maintenance.