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.
journal_name
Proc Natl Acad Sci U S Aauthors
Jankovic V,Ciarrocchi A,Boccuni P,DeBlasio T,Benezra R,Nimer SDdoi
10.1073/pnas.0607894104subject
Has Abstractpub_date
2007-01-23 00:00:00pages
1260-5issue
4eissn
0027-8424issn
1091-6490pii
0607894104journal_volume
104pub_type
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