B-myb is an essential regulator of hematopoietic stem cell and myeloid progenitor cell development

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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2014-02, Vol.111 (8), p.3122-3127
Main Authors: Baker, Stacey J., Ma'ayan, Avi, Lieu, Yen K., John, Premila, Reddy, M. V. Ramana, Chen, Edward Y., Duan, Qiaonan, Snoeck, Hans-Willem, Reddy, E. Premkumar
Format: Article
Language:English
Subjects:
Animals
B lymphocytes
Biological Sciences
Bone Marrow Transplantation
Cell cycle
Cell Cycle Proteins - metabolism
Cell Differentiation - physiology
Crosses, Genetic
DNA Primers - genetics
Embryonic stem cells
Erythroid cells
Flow Cytometry
Gene expression
Genomics
Hematopoiesis - physiology
Hematopoietic stem cells
Hematopoietic Stem Cells - physiology
Immunoblotting
Mice
Mice, Inbred C57BL
Microarray Analysis
Myeloid cells
Myeloid Progenitor Cells - physiology
Pluripotent stem cells
Progenitor cells
Reverse Transcriptase Polymerase Chain Reaction
Stem cells
Trans-Activators - metabolism
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Summary: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 G ₂/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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1315464111