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Endothelial and perivascular cells maintain haematopoietic stem cells

机译：内皮细胞和血管周细胞维持造血干细胞

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摘要

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 Scf~(gfp) 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.
机译：已经提出了几种细胞类型来创建造血干细胞（HSC）的适当位置。但是，HSC维持因子的表达模式尚未得到系统的研究，也没有条件地从任何候选的小生境细胞中删除这种因子。因此，这些因素的细胞来源尚未确定。干细胞因子（SCF；也称为KITL）是维持HSC的关键利基成分。在这里，我们使用Scf〜（gfp）敲入小鼠，发现Scf主要由遍及骨髓的血管周围细胞表达。当有条件地从造血细胞，成骨细胞，表达Nestin-cre或nestin-creER的细胞中删除Scf时，HSC的频率和功能不受影响。但是，当从内皮细胞或表达瘦素受体（Lepr）的血管周围基质细胞中缺失Scf时，HSCs从骨髓中耗尽。当从内皮和表达Lepr的血管周细胞中缺失Scf时，大多数HSC丧失。因此，HSC位于血管周围的环境中，其中多种细胞类型表达促进HSC维持的因子。

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  • 来源
    《Nature》 |2012年第7382期|p.457-462|共6页
  • 作者

    Lei Ding; Thomas L. Saunders; Grigori Enikolopov; Sean J. Morrison;

  • 作者单位

    Howard Hughes Medical Institute, Children's Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.;

    Transgenic Animal Model Core,University of Michigan, Ann Arbor, Michigan 48109-2216, USA.;

    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;

    Howard Hughes Medical Institute, Children's Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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