B-myb is an essential regulator of hematopoietic stem cell and myeloid progenitor cell development
B-myb is an essential regulator of hematopoietic stem cell and myeloid progenitor cell development
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DOI：
10.1073/pnas.1315464111
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发表时间：
2014-02-25
影响因子：
11.1
通讯作者：
Reddy, E. Premkumar
中科院分区：
文献类型：
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作者：
Baker, Stacey J.;Ma'ayan, Avi;Reddy, E. Premkumar
B-myb（MYBL 2）基因是MYB转录因子家族的成员，并且参与细胞周期调节、DNA复制和基因组完整性的维持。然而，其在成人发育和造血过程中的功能尚不清楚。我们在这里表明，在体内的B-myb的条件失活的造血干细胞（HSC）池的耗尽，导致在成熟的淋巴，红细胞和髓细胞的深刻减少。这种缺陷在骨髓中是自发的，并且首先在S和G（2）/M期积累的干细胞中明显。B-myb失活也会导致髓系祖细胞区室的缺陷，包括普通髓系祖细胞的耗竭，但粒细胞-巨噬细胞祖细胞的相对保留。微阵列研究表明，B-myb-null LSK+细胞差异表达指导髓系发育和定型的基因，表明B-myb是控制细胞命运的关键参与者。总的来说，这些研究表明，B-myb是造血过程中造血干细胞和祖细胞的维持和生存所必需的。
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.