Id1 maintains embryonic stem cell self-renewal by up-regulation of nanog and repression of brachyury expression Journal Article

Authors: Romero-Lanman, E. E.; Pavlovic, S.; Amlani, B.; Chin, Y.; Benezra, R.
Article Title: Id1 maintains embryonic stem cell self-renewal by up-regulation of nanog and repression of brachyury expression
Abstract: Understanding the mechanism by which embryonic stem (ES) cells self-renew is crucial for the realization of their therapeutic potential. Earlier, overexpression of Id proteins was shown to be sufficient to maintain mouse ES cells in a self-renewing state even in the absence of serum. Here, we use ES cells derived from Id deficient mice to investigate the requirement for Id proteins in maintaining ES cell self-renewal. We find that Id1 -/- ES cells have a defect in self-renewal and a propensity to differentiate. We observe that chronic or acute loss of Id1 leads to a down-regulation of Nanog, a critical regulator of self-renewal. In addition, in the absence of Id1, ES cells express elevated levels of Brachyury, a marker of mesendoderm differentiation. We find that loss of both Nanog and Id1 is required for the up-regulation of Brachyury, and ectopic Nanog expression in Id1 -/- ES cells rescues the self-renewal defect, indicating that Nanog is the major downstream target of Id1. These results identify Id1 as a critical factor in the maintenance of ES cell self-renewal and suggest a plausible mechanism for its control of lineage commitment. © Copyright 2012, Mary Ann Liebert, Inc. 2012.
Keywords: controlled study; unclassified drug; human cell; nonhuman; cell proliferation; biological markers; animal cell; mouse; animals; mice; mice, knockout; animal tissue; mus; inhibitor of differentiation 1; embryonic stem cell; protein depletion; animal experiment; animal model; rna, small interfering; cell renewal; cell differentiation; homeodomain proteins; cell lineage; gene expression regulation, developmental; embryonic stem cells; plasmids; down regulation; upregulation; inhibitor of differentiation protein 1; up-regulation; transcription factor nanog; culture media; embryo culture techniques; t box transcription factor; t-box domain proteins; protein brachyury; fetal proteins
Journal Title: Stem Cells and Development
Volume: 21
Issue: 3
ISSN: 1547-3287
Publisher: Mary Ann Liebert, Inc  
Date Published: 2012-02-10
Start Page: 384
End Page: 393
Language: English
DOI: 10.1089/scd.2011.0428
PROVIDER: scopus
PUBMED: 22013995
Notes: --- - "Export Date: 1 March 2012" - "CODEN: SCDTA" - "Source: Scopus"
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MSK Authors
  1. Elizabeth E Romero
    3 Romero
  2. Robert Benezra
    133 Benezra
  3. Yvette Chin
    10 Chin
  4. Bhishma Amlani
    1 Amlani