SummaryThe reprogramming factors OCT4, SOX2, KLF4, and MYC (OSKM) can reactivate the pluripotency network in terminally differentiated cells, but also regulate expression of non-pluripotency genes in other contexts, such as the mouse primitive endoderm. The primitive endoderm is an extraembryonic lineage established in parallel to the pluripotent epiblast in the blastocyst, and is the progenitor pool for extraembryonic endoderm stem (XEN) cells. We show that OSKM induce expression of endodermal genes, leading to formation of induced XEN (iXEN) cells, which possess key properties of blastocyst-derived XEN cells, including morphology, transcription profile, self-renewal, and multipotency. Our data show that iXEN cells arise in parallel to induced pluripotent stem cells, indicating that OSKM drive cells to two distinct cell fates during reprogramming.

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Edited by Norma Allewell

Trophoblast stem cells (TSCs) are derived from the early mouse embryo and can substantially contribute to placental development. Two studies by Kubaczka et al. (2015) and Benchetrit et al. (2015) in this issue of Cell Stem Cell now report reprogramming mouse fibroblasts into TSCs, surmounting the first lineage barrier established in development and providing new tools for researching placental specification and diseases.