The 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.

重编程因子OCT4，SOX2，KLF4和MYC（OSKM）可以重新激活终末分化细胞中的多能网络，但在其他情况下（例如小鼠原始内胚层）也可以调节非多能性基因的表达。原始内胚层是与胚泡中多能上皮细胞平行建立的胚外谱系，并且是胚外内胚层干（XEN）细胞的祖细胞库。我们表明OSKM诱导内胚层基因的表达，导致诱导XEN（iXEN）细胞的形成，这些细胞具有囊胚来源的XEN细胞的关键特性，包括形态，转录谱，自我更新和多能性。我们的数据表明，iXEN细胞与诱导的多能干细胞平行出现，表明OSKM在重编程过程中将细胞驱动到两种不同的细胞命运。