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.
authors.affiliation: Molecular Pharmacology and Chemistry Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Jankovic
authors.forename: Alessia
authors.initials: A
authors.lastname: Ciarrocchi
authors.forename: Piernicola
authors.initials: P
authors.lastname: Boccuni
authors.forename: Tony
authors.initials: T
authors.lastname: DeBlasio
authors.forename: Robert
authors.initials: R
authors.lastname: Benezra
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Nimer
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002453:Cell Cycle; D019070:Cell Lineage; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D051798:Inhibitor of Differentiation Protein 1 / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1