The way we were – transcriptional foundations of plasticity in regulative development and differentiation
Plasticity in differentiation is the basis for the remarkable regulative properties of the early mammalian embryo and could underlie regeneration more broadly. I will talk about how transcription factor persistence underlies both plasticity and future potency in differentiation. We have found that in a number of model systems, transcription is directly regulated by signalling, but independently of the transcription factors. The transcription factors remain bound without directly stimulating transcription, but serving to guide signalling responses. In the instance of early differentiation in both embryonic stem cells and embryos, FGF signalling can induce differentiation and exit from pluripotency, however, as long as the transcription factors remain expressed and bound at their sites in enhancers, reversion of this signal produces a regeneration of previous cell states. While we have explored this phenomenon in a number of embryo-based stem cell models, we believe these principles could underlie regeneration more generally.