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

Vladimir Jankovic, Alessia Ciarrocchi, Piernicola Boccuni, Tony DeBlasio, Robert Benezra, Stephen D. Nimer

Research output: Contribution to journalArticle

97 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1260-1265
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number4
DOIs
StatePublished - Jan 23 2007
Externally publishedYes

Keywords

  • Cell fate determination
  • Differentiation
  • Transcriptional regulation

ASJC Scopus subject areas

  • Genetics
  • General

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