Pluripotency Factors in Embryonic Stem Cells Regulate Differentiation into Germ Layers
| Autor: | Zack Smith, Alexander Meissner, Ling-Nan Zou, Matt Thomson, Sharad Ramanathan, Siyuan John Liu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Pluripotent Stem Cells
Cellular differentiation Embryoid body Cell fate determination Biology General Biochemistry Genetics and Molecular Biology Article Mice 03 medical and health sciences 0302 clinical medicine SOX2 Animals Gene Regulatory Networks Induced pluripotent stem cell Cell potency Embryonic Stem Cells 030304 developmental biology Homeodomain Proteins 0303 health sciences Biochemistry Genetics and Molecular Biology(all) Gene Expression Profiling SOXB1 Transcription Factors Gene Expression Regulation Developmental Nanog Homeobox Protein Cell Differentiation Embryonic stem cell Cell biology embryonic structures biological phenomena cell phenomena and immunity Octamer Transcription Factor-3 Germ Layers 030217 neurology & neurosurgery |
| Popis: | SummaryCell 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 |
| Databáze: | OpenAIRE |
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