Douglas Colby

TL;DR: These findings establish a central role for Nanog in the transcription factor hierarchy that defines ES cell identity and confirm that Cytokine dependence, multilineage differentiation, and embryo colonization capacity are fully restored upon transgene excision.

TL;DR: By genetic deletion, it is shown that, although they are prone to differentiate, embryonic stem cells can self-renew indefinitely in the permanent absence of Nanog, and it is surmised that Nanog stabilizes embryonicstem cells in culture by resisting or reversing alternative gene expression states.

TL;DR: Investigation of ESCs expressing different Nanog levels and Nanog−/− cells with distinct functionally inducible Nanog proteins to identify Nanog-responsive genes finds Esrrb deletion abolishes the defining ability of Nanog to confer LIF-independent ESC self-renewal.

TL;DR: It is shown that ESCs with reduced Oct4 expression resulting from heterozygosity also exhibit a stabilized pluripotent state and that the wild-type Oct4 concentration range enables effective differentiation.

TL;DR: It is concluded that the architecture of the pluripotency gene regulatory network encodes the capacity to generate reversible states of Nanog transcription via a Nanog‐centred autorepressive loop, and cellular variability in self‐renewal efficiency is an emergent property of the stem cell regulatory network.