Heightened potency of human pluripotent stem cell lines created by transient BMP4 exposure

Significance Human ES cells (ESCs) and induced pluripotent stem cells (iPSCs) can differentiate along all the major cell lineages of the embryo proper, but there is evidence that they can also give rise to extraembryonic placental trophoblast. This observation is controversial because human ESCs (hESCs) are considered to arise from a part of the embryo that does not contribute to trophoblast. Here, we describe stable, self-renewing stem cell lines derived from hESCs and iPSCs by brief exposure to bone morphogenetic protein 4 (BMP4) that appear poised to differentiate readily along all the main developmental cell lineages, including placental trophoblast. BMP4 signaling may thus play a role in the early embryo by establishing a cell state permissive for trophoblast development.