Cell fate decision by a morphogen-transcription factor-chromatin modifier axis

Abstract

Cell fate decision remains poorly understood at the molecular level. Embryogenesis provides a unique opportunity to analyse molecular details associated cell fate decisions. Works based on model organisms have provided a conceptual framework of genes that specify cell fate control, for example, transcription factors or TFs controlling processes from pluripotency to immunity1. How TFs specify cell fate remains unknown. Here we report that Sall4 relies on NuRD or nucleosome-remodeling and deacetylase complex to interpret BMP4 signal to decide cell fates in a well-controlled system in vitro. While NuRD complex cooperates with SALL4 to convert mouse embryonic fibroblast or MEFs to pluripotency, BMP4 diverts the same process to an alternative fate, PrE or primitive endoderm. Mechanistically, BMP4 signals the dissociation of Sall4 from NuRD physically to establish a gene regulatory network for PrE. Our results provide a conceptual framework to explore the rich landscapes of cell fate choices intrinsic to development in higher organisms involving morphogen-TF-chromatin modifier pathways.