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Totipotent embryonic stem cells arise in ground-state culture conditions.

TitleTotipotent embryonic stem cells arise in ground-state culture conditions.
Publication TypeJournal Article
Year of Publication2013
AuthorsMorgani SM, Canham MA, Nichols J, Sharov AA, Migueles RPortero, Ko MSH, Brickman JM
JournalCell Rep
Date Published2013 Jun 27
KeywordsAnimals, Cell Differentiation, Cells, Cultured, Embryonic Stem Cells, Female, Humans, Mice, Mice, Inbred C57BL, Mice, Transgenic, Pseudopregnancy, Totipotent Stem Cells

Embryonic stem cells (ESCs) are derived from mammalian embryos during the transition from totipotency, when individual blastomeres can make all lineages, to pluripotency, when they are competent to make only embryonic lineages. ESCs maintained with inhibitors of MEK and GSK3 (2i) are thought to represent an embryonically restricted ground state. However, we observed heterogeneous expression of the extraembryonic endoderm marker Hex in 2i-cultured embryos, suggesting that 2i blocked development prior to epiblast commitment. Similarly, 2i ESC cultures were heterogeneous and contained a Hex-positive fraction primed to differentiate into trophoblast and extraembryonic endoderm. Single Hex-positive ESCs coexpressed epiblast and extraembryonic genes and contributed to all lineages in chimeras. The cytokine LIF, necessary for ESC self-renewal, supported the expansion of this population but did not directly support Nanog-positive epiblast-like ESCs. Thus, 2i and LIF support a totipotent state comparable to early embryonic cells that coexpress embryonic and extraembryonic determinants.

Alternate JournalCell Rep
PubMed ID23746443
PubMed Central IDPMC3701323
Grant List079249 / / Wellcome Trust / United Kingdom
G0701428 / / Medical Research Council / United Kingdom
G0701429 / / Medical Research Council / United Kingdom
Z01AG AG000656 / AG / NIA NIH HHS / United States
Z01AG000662 / AG / NIA NIH HHS / United States