Id1 restrains myeloid commitment, maintaining the self-renewal capacity of hematopoietic stem cells Journal Article


Authors: Jankovic, V.; Ciarrocchi, A.; Boccuni, P.; Deblasio, T.; Benezra, R.; Nimer, S. D.
Article Title: Id1 restrains myeloid commitment, maintaining the self-renewal capacity of hematopoietic stem cells
Abstract: Appropriate hematopoietic stem cell (HSC) self-renewal reflects the tight regulation of cell cycle entry and lineage commitment. Here, we show that Id1, a dominant-negative regulator of E protein transcription factors, maintains HSC self-renewal by preserving the undifferentiated state. Id1-deficient HSCs show increased cell cycling, by BrdU incorporation in vivo, but fail to efficiently self-renew, leading to low steady-state HSC numbers and premature exhaustion in serial bone marrow transplant assays. The increased cycling reflects the perturbed differentiation process, because Id1 null HSCs more readily commit to myeloid differentiation, with inappropriate expression of myeloerythroid- specific genes. Thus, Id1 appears to regulate the fate of HSCs by acting as a true inhibitor of differentiation. © 2007 by The National Academy of Sciences of the USA.
Keywords: controlled study; nonhuman; animal cell; mouse; animals; mice; cell cycle; gene expression; inhibitor of differentiation 1; animal experiment; animal model; cell fate; cell renewal; cell differentiation; cell assay; mice, inbred c57bl; cell lineage; transcription regulation; hematopoietic stem cells; cell count; bone marrow cell; hematopoietic stem cell; inhibitor of differentiation protein 1; bone marrow transplantation; differentiation; transcriptional regulation; broxuridine; cell fate determination
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 104
Issue: 4
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2007-01-23
Start Page: 1260
End Page: 1265
Language: English
DOI: 10.1073/pnas.0607894104
PUBMED: 17227850
PROVIDER: scopus
PMCID: PMC1783103
DOI/URL:
Notes: --- - "Cited By (since 1996): 48" - "Export Date: 17 November 2011" - "CODEN: PNASA" - "Source: Scopus"
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MSK Authors
  1. Piernicola Boccuni
    16 Boccuni
  2. Stephen D Nimer
    347 Nimer
  3. Robert Benezra
    146 Benezra