Thomson M, Liu SJ, Zou LN, Smith Z, Meissner A, Ramanathan S. Pluripotency factors in embryonic stem cells regulate differentiation into germ layers. Cell. 2011 Jun 10; 145(6):875-89.

Citation

Thomson M, Liu SJ, Zou LN, Smith Z, Meissner A, Ramanathan S. 2011. Pluripotency factors in embryonic stem cells regulate differentiation into germ layers. Cell. 145(6):875-89. Pubmed: 21663792 DOI:10.1016/j.cell.2011.05.017

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.

Related Faculty

Alexander Meissner, Ph.D.

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

Sharad Ramanathan, Ph.D.

Ramanathan Lab

Sharad Ramanathan investigates how multi-potent stem cells make fate decisions to give rise to complex human tissues, and how the dynamics of key neurons in the nervous system drive behavioral decisions.