Nakauchi H, Oguro H, Negishi M, Iwama A
Laboratory of Stem Cell Therapy, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Japan.
Ernst Schering Res Found Workshop. 2005(54):85-100. doi: 10.1007/3-540-37644-5_6.
The Polycomb group (PcG) gene Bmi-1 has recently been implicated in the maintenance of hematopoietic stem cells (HSCs). However, the role of each component of PcG complex in HSCs and the impact of forced expression of PcG genes on stem cell self-renewal remain to be elucidated. To address these issues, we performed both loss-of-function and gain-of-function analysis on various PcG proteins. Expression analysis revealed that not only Bmi-1 but also other PcG genes are predominantly expressed in HSCs. Loss-of-function analyses, however, demonstrated that absence of Bmi-1 is preferentially linked with a profound defect in HSC self-renewal, indicating a central role for Bmi-1, but not the other components, in the maintenance of HSC self-renewal. Over-expression analysis of PcG genes also confirmed an important role of Bmi-1 in HSC self-renewal. Our findings indicate that the expression level of Bmi-1 is the critical determinant for the self-renewal capacity of HSCs. These findings uncover novel aspects of stem cell regulation exerted through epigenetic modifications by the PcG proteins.
多梳蛋白家族（PcG）基因Bmi-1最近被认为与造血干细胞（HSC）的维持有关。然而，PcG复合体各组分在造血干细胞中的作用以及PcG基因的强制表达对干细胞自我更新的影响仍有待阐明。为了解决这些问题，我们对各种PcG蛋白进行了功能缺失和功能获得分析。表达分析表明，不仅Bmi-1，其他PcG基因也主要在造血干细胞中表达。然而，功能缺失分析表明，Bmi-1的缺失与造血干细胞自我更新的严重缺陷优先相关，这表明Bmi-1而非其他组分在维持造血干细胞自我更新中起核心作用。PcG基因的过表达分析也证实了Bmi-1在造血干细胞自我更新中的重要作用。我们的研究结果表明，Bmi-1的表达水平是造血干细胞自我更新能力的关键决定因素。这些发现揭示了通过PcG蛋白的表观遗传修饰对干细胞调控的新方面。
