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.
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Publication status||Published - Jan 23 2007|
- Cell fate determination
- Transcriptional regulation
ASJC Scopus subject areas