Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1
Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1
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DOI：
10.1016/j.immuni.2004.11.004
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发表时间：
2004-12-01
期刊：
影响因子：
32.4
通讯作者：
Nakauchi, H
中科院分区：
文献类型：
--
作者：
Iwama, A;Oguro, H;Nakauchi, H
Polycomb组（PcG）基因Bmi-1最近被牵涉在造血干细胞（HSC）的维持中，免于功能丧失分析。在这里，我们证明Bmi-1的表达增加促进HSC自我更新。Bmi-1的强制表达增强了HSC的对称细胞分裂，并介导了通过细胞分裂遗传干细胞的更高可能性。相应地，Bmi-1，而不是其他PcG基因的强制表达，导致了显着的多能祖细胞的体外扩增和显着增强的HSC体内重建能力。功能丧失分析显示，在PcG基因中，Bmi-1的缺失优先与HSC自我更新的严重缺陷相关。我们的研究结果将Bmi-1定义为HSC自我更新的核心参与者，并证明Bmi-1是HSC治疗操作的靶点。
The Polycomb group (PcG) gene Bmi-1 has recently been implicated in the maintenance of hematopoietic stem cells (HSC) from loss-of-function analysis. Here, we demonstrate that increased expression of Bmi-1 promotes HSC self-renewal. Forced expression of Bmi-1 enhanced symmetrical cell division of HSCs and mediated a higher probability of inheritance of stemness through cell division. Correspondingly, forced expression of Bmi-1, but not the other PcG genes, led to a striking ex vivo expansion of multipotential progenitors and marked augmentation of HSC repopulating capacity in vivo. Loss-of-function analyses revealed that among PcG genes, absence of Bmi-1 is preferentially linked With a profound defect in HSC self-renewal. Our findings define Bmi-1 as a central player in HSC self-renewal and demonstrate that Bmi-1 is a target for therapeutic manipulation of HSCs.