Nature：首次揭示维持造血干细胞微环境的关键细胞因子来源

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Nature：首次揭示维持造血干细胞微环境的关键细胞因子来源  关注儿童辅食批发，有帮助！

       

        近期美国科学家在新研究中利用一种系统性的条件遗传学方法，对体内造血干细胞生存及生长的小环境进行了鉴别，由此识别出了维持造血干细胞小环境必需的干细胞因子的细胞来源。新研究发现将帮助研究人员鉴别出促进干细胞维持和增殖的细胞及其功能机制。相关论文发表在《自然》(Nature)杂志上。并且Ilya A. Shestopalov和Leonard I. Zon针对此项研究发表了一篇评论性文章《干细胞：合适的邻居》。

        尽管近年来科学家们已确定了大量干细胞的生成及分化机制，然而在造血干细胞制造研究领域却仍然进展缓慢。其中一个关键性的障碍就是对于体内造血干细胞所处的微环境(niche)知之甚少。

        研究人员通过系统性地确定哪些细胞是干细胞因子(stem cell factor, SCF)—— 维持造血干细胞所需的蛋白——的来源而解决了这种问题。研究小组用来自水母的表达绿色荧光蛋白的基因交换小鼠中表达干细胞因子的基因。发绿光的细胞是内皮细胞和血管周细胞，从而揭示它们就是培育健康造血干细胞的微环境的产生者。

        另外实验室研究还表明如果干细胞因子从内皮细胞或血管周细胞中去除，则会导致造血干细胞耗竭。如果内皮细胞和血管周细胞中的干细胞因子都丢失，则会导致造血干细胞几乎完全消失。

        新研究发现表明造血干细胞存在于一个血管周围的小环境中，在该小环境中，多种细胞类型表达能够促进其维持的因子。

        主要研究人员，成体干细胞领域的权威科学家Sean J. Morrison说：“数十年来科学家们一直致力于探究干细胞小环境，然而这是研究人员第一次真正揭示出对维持体内造血干细胞微环境起关键性作用的细胞。新研究发现将帮助研究人员鉴别出促进干细胞维持和增殖的细胞及其功能机制。”
       
        原文链接：Endothelial and perivascular cells maintain haematopoietic stem cells

        原文摘要：

        Endothelial and perivascular Cells maintain haematopoietic stem cells

        Several cell types have been proposed to create niches for haematopoietic stem cells (HSCs). However, the expression patterns of HSC maintenance factors have not been systematically studied and no such factor has been conditionally deleted from any candidate niche cell. Thus, the cellular sources of these factors are undetermined. Stem cell factor (SCF; also known as KITL) is a key niche component that maintains HSCs. Here, using Scfgfp knock-in mice, we found that Scf was primarily expressed by perivascular cells throughout the bone marrow. HSC frequency and function were not affected when Scf was conditionally deleted from haematopoietic cells, osteoblasts, nestin-cre- or nestin-creER-expressing cells. However, HSCs were depleted from bone marrow when Scf was deleted from endothelial cells or leptin receptor (Lepr)-expressing perivascular stromal cells. Most HSCs were lost when Scf was deleted from both endothelial and Lepr-expressing perivascular cells. Thus, HSCs reside in a perivascular niche in which multiple cell types express factors that promote HSC maintenance.