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

被引:39
作者
Baker, Stacey J. [1 ]
Ma'ayan, Avi [2 ]
Lieu, Yen K. [1 ]
John, Premila [4 ]
Reddy, M. V. Ramana [1 ]
Chen, Edward Y. [2 ]
Duan, Qiaonan [2 ]
Snoeck, Hans-Willem [1 ]
Reddy, E. Premkumar [1 ,3 ]
机构
[1] Icahn Sch Med Mt Sinai, Dept Oncol Sci, New York, NY 10029 USA
[2] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA
[3] Icahn Sch Med Mt Sinai, Dept Biol Struct, New York, NY 10029 USA
[4] Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19140 USA
基金
美国国家卫生研究院;
关键词
myeloipiesis; myelodisplastic syndrome; C-MYB; TRANSCRIPTION FACTOR; SELF-RENEWAL; S-PHASE; MYELODYSPLASTIC SYNDROMES; LINEAGE COMMITMENT; CYCLE REGULATION; GENE-EXPRESSION; DIFFERENTIATION; IDENTIFICATION;
D O I
10.1073/pnas.1315464111
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:3122 / 3127
页数:6
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