Citation

Abstract

Cell fate decisions are fundamental for development, but we do not know how transcriptional networks reorganize during the transition from a pluripotent to a differentiated cell state. Here, we asked how mouse embryonic stem cells (ESCs) leave the pluripotent state and choose between germ layer fates. By analyzing the dynamics of the transcriptional circuit that maintains pluripotency, we found that Oct4 and Sox2, proteins that maintain ESC identity, also orchestrate germ layer fate selection. Oct4 suppresses neural ectodermal differentiation and promotes mesendodermal differentiation; Sox2 inhibits mesendodermal differentiation and promotes neural ectodermal differentiation. Differentiation signals continuously and asymmetrically modulate Oct4 and Sox2 protein levels, altering their binding pattern in the genome, and leading to cell fate choice. The same factors that maintain pluripotency thus also integrate external signals and control lineage selection. Our study provides a framework for understanding how complex transcription factor networks control cell fate decisions in progenitor cells.
Copyright © 2011 Elsevier Inc. All rights reserved.

Related Faculty

Photo of Alex Meissner

The Meissner laboratory uses genomic tools to study stem cell biology with a particular focus on epigenetic reprogramming.

Photo of Sharad Ramanathan

Sharad Ramanathan studies how the dynamics of the underlying circuits allow cells and organisms to make decisions. To do so he brings together Biology with tools from Applied Math, Microscopy and Microfluidics.

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