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

96 Citations (Scopus)

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
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
Publication statusPublished - Jan 23 2007

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Hematopoietic Stem Cells
Cell Lineage
Bromodeoxyuridine
Cell Cycle
Transcription Factors
Cell Count
Bone Marrow
Transplants
Genes
Proteins
Cell Self Renewal

Keywords

  • Cell fate determination
  • Differentiation
  • Transcriptional regulation

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Id1 restrains myeloid commitment, maintaining the self-renewal capacity of hematopoietic stem cells. / Jankovic, Vladimir; Ciarrocchi, Alessia; Boccuni, Piernicola; DeBlasio, Tony; Benezra, Robert; Nimer, Stephen D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 4, 23.01.2007, p. 1260-1265.

Research output: Contribution to journalArticle

Jankovic, Vladimir ; Ciarrocchi, Alessia ; Boccuni, Piernicola ; DeBlasio, Tony ; Benezra, Robert ; Nimer, Stephen D. / Id1 restrains myeloid commitment, maintaining the self-renewal capacity of hematopoietic stem cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 4. pp. 1260-1265.
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