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HYPOTHESIS 3
Development 138, 3-8 (2011) doi:10.1242/dev.050831
© 2011. Published by The Company of Biologists Ltd
The origin and identity of embryonic stem cells
Jennifer Nichols1,2,* and Austin Smith1,3
Summary cells can be derived in explant cultures via two routes: directly
Embryonic stem (ES) cells are used extensively in biomedical from the newly formed epiblast, as it transits the state of naïve
research and as a model with which to study early mammalian pluripotency; or during the specification of PGCs in culture when
development, but their exact origin has been subject to much cells undergo epigenetic reprogramming, resulting in their re-
debate. They are routinely derived from pre-implantation acquisition of pluripotency (Fig. 1).
embryos, but it has been suggested that the cells that give rise
to ES cells might arise from epiblast cells that are already Emergence of naïve pluripotency
predisposed to a primordial germ cell (PGC) fate, which then Fertilisation in mammals produces a zygote that will give rise to
progress to ES cell status via the PGC lineage. Based on recent the entire embryo and to the extra-embryonic lineages. Equipotent
findings, we propose here that ES cells can be derived directly blastomeres are produced from the zygote during several rounds of
from early epiblast cells and that ES cells might arise via two cleavage divisions, but by the blastocyst stage, two distinct lineages
different routes that are dictated by their culture conditions. have emerged th
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