成年干细胞的表观控制.docxVIP

成年干细胞的表观控制Nature：成年干细胞的表观控制作者：Nature来源：Nature2013-8-23 10:04:41分享到：1关键词： 造血干细胞Linheng Li及同事完成的一项新的研究工作研究的是，造血干细胞中H19“差异化甲基化区域” (H19-DMR) 的删除所产生的效应。DMR已知控制印记基因H19 和 Igf2从H19–Igf2 位点的表达，将H19 的表达限制于母方等位基因，将Igf2的表达限制于父方等位基因。作者报告了一系列由母方表达的生长限制印记基因在“长期造血干细胞”(LT-HSCs)中、而不是在增殖中的短期HSCs中的优势表达，说明基因组印记在维持静态LT-HSCs中起一个关键作用。生物谷推荐英文摘要：Nature???doi:10.1038/nature12303Maternal imprinting at the H19–Igf2 locus maintains adult haematopoietic stem cell quiescenceAparna Venkatraman,? Xi C. He,? Joanne L. Thorvaldsen,Ryohichi Sugimura,? John M. Perry, Fang Tao,Meng Zhao,Matthew K. Christenson, Rebeca Sanchez,? Jaclyn Y. Yu,Lai Peng, Jeffrey S. Haug,Ariel Paulson,?Hua Li,Xiao-bo Zhong,Thomas L. Clemens,Marisa S. Bartolomei? Linheng LiThe epigenetic regulation of imprinted genes by monoallelic DNA methylation of either maternal or paternal alleles is critical for embryonic growth and development. Imprinted genes were recently shown to be expressed in mammalian adult stem cells to support self-renewal of neural and lung stem cells; however, a role for imprinting per se in adult stem cells remains elusive. Here we show upregulation of growth-restricting imprinted genes, including in the H19–Igf2 locus, in long-term haematopoietic stem cells and their downregulation upon haematopoietic stem cell activation and proliferation. A differentially methylated region upstream of H19 (H19-DMR), serving as the imprinting control region, determines the reciprocal expression of H19 from the maternal allele and Igf2 from the paternal allele. In addition, H19 serves as a source of miR-675, which restricts Igf1r expression. We demonstrate that conditional deletion of the maternal but not the paternal H19-DMR reduces adult haematopoietic stem cell quiescence, a state required for long-term maintenance of haematopoietic stem cells, and compromises haematopoietic stem cell function. Maternal-specific H19-DMR deletion results in activation of the Igf2–Igfr1 pathway, as shown by the translocation of phosphoryla