摘要：SummaryInduced pluripotency provides a tool to explore mechanisms underlying establishment, maintenance, and differentiation of naive pluripotent stem cells (nPSCs). Here, we report that self-renewal of nPSCs requires minimal Sox2 expression (Sox2-low). Sox2-low nPSCs do not show impaired neuroectoderm specification and differentiate efficientlyin vitrointo all embryonic germ lineages. Strikingly, upon the removal of self-renewing cues Sox2-low nPSCs differentiate into both embryonic and extraembryonic cell fatesin vitroandin vivo. This differs from previous studies which only identified conditions that allowed cells to differentiate to one fate or the other. At the single-cell level self-renewing Sox2-low nPSCs exhibit a naive molecular signature. However, they display a nearer trophoblast identity than controls and decreased ability of Oct4 to bind naïve-associated regulatory sequences. In sum, this work defines wild-type levels of Sox2 as a restrictor of developmental potential and suggests perturbation of naive network as a mechanism to increase cell plasticity.Graphical abstractDisplay OmittedHighlights•Low Sox2 expression is sufficient for naive pluripotent stem cell self-renewal•Low Sox2 expression does not impair neurectoderm differentiationin vitro•Low Sox2 expression impairs Oct4 genomic occupancy•Low Sox2 increases naive pluripotent stem cell plasticityin vitroandin vivoBiological Sciences; Cell Biology; Stem Cells Research
