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  Control of early fate decisions in human ES cells by distinct states of TGFβ pathway activity

Greber, B., Lehrach, H., & Adjaye, J. (2008). Control of early fate decisions in human ES cells by distinct states of TGFβ pathway activity. Stem Cells and Development, 17(6), 1065-1077. doi:10.1089/scd.2008.0035.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7E9C-F Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7E9D-D
Genre: Journal Article
Alternative Title : Stem Cells Dev

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 Creators:
Greber, Boris1, Author
Lehrach, Hans2, Author              
Adjaye, James3, Author              
Affiliations:
1Max Planck Society, ou_persistent13              
2Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              
3Molecular Embryology and Aging (James Adjaye), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479654              

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 Abstract: The mechanisms controlling self-renewal versus lineage commitment in human embryonic stem (hES) cells are not well understood. Nonetheless, current knowledge suggests a crucial role for TGFβ signaling in controlling these early fate decisions. We have investigated the effects of TGFβ pathway activation and inhibition on gene expression in hES cells. Our data reveal that SMAD 2/3 signaling directly supports NANOG expression, while SMAD 1/5/8 activation moderately represses SOX2. In addition, genes encoding key developmentally relevant signaling molecules and transcription factors appear to be immediately downstream of SMAD 1/5/8 signaling, or require both SMAD 1/5/8 and 2/3 activation, or inactivation of TGFβ signaling for their induction. Defined stimulation/inhibition of the two TGFβ branches appeared to control early fate decisions in accordance with these downstream transcriptional effects. Our results therefore help to better understand how pluripotency is mediated at the transcriptional level.

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Language(s): eng - English
 Dates: 2008-12-01
 Publication Status: Published in print
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Title: Stem Cells and Development
  Alternative Title : Stem Cells Dev
Source Genre: Journal
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Publ. Info: -
Pages: - Volume / Issue: 17 (6) Sequence Number: - Start / End Page: 1065 - 1077 Identifier: ISSN: 1547-3287