Pluripotent Stem Cell Microenvironment

During generation of pluripotent epiblast within the mammalian preimplantation embryo, specification of extraembryonic lineages such as trophectoderm (TE) and primitive endoderm (PrE) is proceeding at the same time. Pluripotent cells appear to be mutually interacting with these neighboring extraembryonic cells that are dynamically changing in a short period of time relative to somatic stem cells. Indeed, environmental cues provided by TE and PrE are shown to be indispensable for normal epiblast development. Under certain conditions, pluripotent cells can be propagated indefinitely in vitro maintaining their differentiation potential. Interestingly, within established cultures of such pluripotent stem cells (PSCs), we can observe dynamically interconverting subfractions, which seem to represent specific lineages within the early embryo such as PrE and epiblast. Furthermore, cellular interplays between the PSC subfractions are critical for self-renewal of PSCs without neoplastic transformation, suggesting a pivotal role for the autologously generated PSC niche in the maintenance of pluripotency and culture homeostasis.