Supporting data for <i>“TP53 is required for trophoblast lineage development from human expanded potential stem cells”</i>

This dataset covers the major findings of the investigation of p53 functions in human trophoblast development. In this dataset, it is presented that heterogenous expression of p53 in human expanded stem cells (EPSCs) is associated with cell cycle state and trophoblast differentiation potential. By generating p53-null human EPSCs, it was demonstrated that p53 deficiency compromised trophoblast differentiation and impaired trophoblast functions including the ability to secret pregnancy-associated hormone and the ability to implant. Transcriptomic analysis suggested hyperactivation of ERK/MAPK signaling upon loss of p53, and inhibition of ERK proteins restored the trophoblast differentiation potential from p53-null human EPSCs. Furthermore, in the established human trophoblast stem cells (TSCs), loss of p53 altered global chromatin accessibility, regions of which were enriched for motifs for trophoblast master regulators. As a consequence, p53-null human TSCs exhibited compromised differentiation potential into trophoblast sub-lineages. More importantly, <i>in vivo</i> mouse early pre-implantation embryonic model further underscored the importance of p53 in trophectoderm lineage development. The study present here has uncovered a novel role of p53 in human trophoblast development and carries novel insights for clinical applications.