Pluripotency factors in embryonic stem cells regulate differentiation into germ layers

Matt Thomson, Siyuan John Liu, Ling Nan Zou, Zack Smith, Alexander Meissner, Sharad Ramanathan

Research output: Contribution to journalArticle

338 Scopus citations

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. PaperClip:

Original languageEnglish (US)
Pages (from-to)875-889
Number of pages15
JournalCell
Volume145
Issue number6
DOIs
StatePublished - Jun 10 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Thomson, M., Liu, S. J., Zou, L. N., Smith, Z., Meissner, A., & Ramanathan, S. (2011). Pluripotency factors in embryonic stem cells regulate differentiation into germ layers. Cell, 145(6), 875-889. https://doi.org/10.1016/j.cell.2011.05.017