HAND1, partially mediated through ape-specific LTR binding, is essential for human extra-embryonic mesenchyme derivation from iPSCs.

ABSTRACT: The specification of extra-embryonic mesenchyme (ExMC) is a prime example of developmental divergence between mouse and human. Derived from definitive mesoderm during mouse gastrulation, the human ExMC first appears at peri-implantation prior to gastrulation and therefore its human cellular origin, still unknown, must differ. In a human pluripotent stem cell model, we report that ExMC shares progenitor cells with trophoblast, suggesting a trophectoderm origin. This ability to form ExMC appears to extend to human trophoblast stem cell lines. We define HAND1 as an essential regulator of ExMC specification, with null cells remaining in the trophoblast lineage. Bound by HAND1, ape-specific, endogenous retrovirus-derived LTR2B contributes to unique features of ExMC. Additionally, ExMC supports

SUBMITTER: Liu Z 

PROVIDER: S-EPMC12082684 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature