A common molecular logic determines embryonic stem cell self-renewal and reprogramming.

ABSTRACT: During differentiation and reprogramming, new cell identities are generated by reconfiguration of gene regulatory networks. Here, we combined automated formal reasoning with experimentation to expose the logic of network activation during induction of naïve pluripotency. We find that a Boolean network architecture defined for maintenance of naïve state embryonic stem cells (ESC) also explains transcription factor behaviour and potency during resetting from primed pluripotency. Computationally identified gene activation trajectories were experimentally substantiated at single-cell resolution by RT-qPCR Contingency of factor availability explains the counterintuitive observation that Klf2, which is dispensable for ESC maintenance, is required during resetting. We tested 124 predictions formu

SUBMITTER: Dunn SJ 

PROVIDER: S-EPMC6316172 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature