title: B-myb is an essential regulator of hematopoietic stem cell and myeloid progenitor cell development.
abstract: The B-myb (MYBL2) gene is a member of the MYB family of transcription factors and is involved in cell cycle regulation, DNA replication, and maintenance of genomic integrity. However, its function during adult development and hematopoiesis is unknown. We show here that conditional inactivation of B-myb in vivo results in depletion of the hematopoietic stem cell (HSC) pool, leading to profound reductions in mature lymphoid, erythroid, and myeloid cells. This defect is autonomous to the bone marrow and is first evident in stem cells, which accumulate in the S and G2/M phases. B-myb inactivation also causes defects in the myeloid progenitor compartment, consisting of depletion of common myeloid progenitors but relative sparing of granulocyte-macrophage progenitors. Microarray studies indicate that B-myb-null LSK(+) cells differentially express genes that direct myeloid lineage development and commitment, suggesting that B-myb is a key player in controlling cell fate. Collectively, these studies demonstrate that B-myb is essential for HSC and progenitor maintenance and survival during hematopoiesis.
authors: Department of Oncological Sciences, Department of Pharmacology and Systems Therapeutics, and Departments of Oncological Sciences and Structural Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
authors: Stacey J
authors: SJ
authors: Baker
authors: Avi
authors: A
authors: Ma'ayan
authors: Yen K
authors: YK
authors: Lieu
authors: Premila
authors: P
authors: John
authors: M V Ramana
authors: MV
authors: Reddy
authors: Edward Y
authors: EY
authors: Chen
authors: Qiaonan
authors: Q
authors: Duan
authors: Hans-Willem
authors: HW
authors: Snoeck
authors: E Premkumar
authors: EP
authors: Reddy
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D003433:Crosses, Genetic; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D015151:Immunoblotting; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D023461:Myeloid Progenitor Cells / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D017931:DNA Primers; C499306:Mybl2 protein, mouse; D015534:Trans-Activators
keywords: myelodisplastic syndrome; myeloipiesis