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【分享】在多种组织中，Prdm16通过部分调节氧化压力来增加干细胞的持续性
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Prdm16 promotes stem cell maintenance in multiple tissues, partly by regulating oxidative stress 在多种组织中，Prdm16通过部分调节氧化压力来增加干细胞的持续性 Sergei Chuikov1,2,3,5, Boaz P. Levi1,2,3,5, Michael L. Smith1,2,3 and Sean J. Morrison1,2,3,4 1Howard Hughes Medical Institute, 2Department of Internal Medicine, 3Center for Stem Cell Biology, Life Sciences Institute, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI 48109-2216, USA. nature cell biology VOLUME 12 | NUMBER 10 | OCTOBER 2010 摘要：To better understand the mechanisms that regulate stem cell identity and function, we sought to identify genes that are preferentially expressed by stem cells and critical for their function in multiple tissues. Prdm16 is a transcription factor that regulates leukaemogenesis1, palatogenesis2 and brown-fat development3–5, but which was not known to be required for stem cell function. We demonstrate that Prdm16 is preferentially expressed by stem cells throughout the nervous and haematopoieticsystems and is required for their maintenance. In the haematopoieticand nervous systems, Prdm16 deficiency led to changes in the levels of reactive oxygen species (ROS), depletion of stem cells, increased cell death and altered cell-cycle distribution. In neural stem/progenitor cells, Prdm16 binds to the Hgfpromoter, and Hgfexpression declined in the absence of Prdm16. Addition of recombinant HGF to Prdm16-deficient neural stem cells in cell culture reduced the depletion of these cells and partially rescued the increase in ROS levels. Administration of the anti-oxidant, N-acetyl-cysteine, to Prdm16-deficient mice partially rescued defects in neural stem/progenitor cell function and neural development. Prdm16 therefore promotes stem cell maintenance in multiple tissues, partly by modulating oxidative stress. 1.为了理解调节干细胞功能的机制，作者寻找了很多基因，这些基因优先在干细胞中表达并且对于它们在多种组织中的功能起着至关重要的作用。 2. Prdm16 是一种转录因子，它调节着腭的发生，棕色脂肪的发生，但是还不知道这些是干细胞行使功能所需要的。 3.在造血系统和神经系统中，Prdm16的缺失会导致ROS水平的改变，干细胞的缺失，增加细胞死亡率和改变细胞周期的分布。 4.在神经干细胞和祖细胞中，Prdm16 是和Hgf启动子相结合的，并且当缺少Prdm16 时，Hgf的表达量降低。 5.在缺少Prdm16的神经干细胞中加入重组的HGF会降低干细胞的死亡同时能部分恢复ROS水平的增加。 更多资料请查看www.bioknow.cn |
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