Pluripotency factors in embryonic stem cells regulate differentiation into germ layers

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

Research output: Contribution to journalArticle

303 Citations (Scopus)

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

Fingerprint

Germ Layers
Embryonic Stem Cells
Stem cells
Cell Differentiation
Proteins
Transcription Factors
Genes
Networks (circuits)
Gene Regulatory Networks
Stem Cells
Genome

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Thomson, M., Liu, S. J., Zou, L., 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
Thomson, Matt ; Liu, Siyuan John ; Zou, Ling-nian ; Smith, Zack ; Meissner, Alexander ; Ramanathan, Sharad. / Pluripotency factors in embryonic stem cells regulate differentiation into germ layers. In: Cell. 2011 ; Vol. 145, No. 6. pp. 875-889.
@article{6bbdab6ce1bb428d855ce7e3f36f29b1,
title = "Pluripotency factors in embryonic stem cells regulate differentiation into germ layers",
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:",
author = "Matt Thomson and Liu, {Siyuan John} and Ling-nian Zou and Zack Smith and Alexander Meissner and Sharad Ramanathan",
year = "2011",
month = "6",
day = "10",
doi = "10.1016/j.cell.2011.05.017",
language = "English (US)",
volume = "145",
pages = "875--889",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "6",

}

Thomson, M, Liu, SJ, Zou, L, Smith, Z, Meissner, A & Ramanathan, S 2011, 'Pluripotency factors in embryonic stem cells regulate differentiation into germ layers', Cell, vol. 145, no. 6, pp. 875-889. https://doi.org/10.1016/j.cell.2011.05.017

Pluripotency factors in embryonic stem cells regulate differentiation into germ layers. / Thomson, Matt; Liu, Siyuan John; Zou, Ling-nian; Smith, Zack; Meissner, Alexander; Ramanathan, Sharad.

In: Cell, Vol. 145, No. 6, 10.06.2011, p. 875-889.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pluripotency factors in embryonic stem cells regulate differentiation into germ layers

AU - Thomson, Matt

AU - Liu, Siyuan John

AU - Zou, Ling-nian

AU - Smith, Zack

AU - Meissner, Alexander

AU - Ramanathan, Sharad

PY - 2011/6/10

Y1 - 2011/6/10

N2 - 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:

AB - 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:

UR - http://www.scopus.com/inward/record.url?scp=79958263080&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79958263080&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2011.05.017

DO - 10.1016/j.cell.2011.05.017

M3 - Article

C2 - 21663792

AN - SCOPUS:79958263080

VL - 145

SP - 875

EP - 889

JO - Cell

JF - Cell

SN - 0092-8674

IS - 6

ER -