Howard Hughes Medical Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Nature. 2012 Jan 25;481(7382):457-62. doi: 10.1038/nature10783.
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.
已经提出了几种细胞类型来为造血干细胞（HSCs）创造龛位。然而，HSC 维持因子的表达模式尚未得到系统研究，也没有任何候选龛位细胞中对这些因子进行条件性删除。因此，这些因子的细胞来源尚未确定。干细胞因子（SCF；也称为 KITL）是维持 HSCs 的关键龛位成分。在这里，我们使用 Scf(gfp) 敲入小鼠发现，Scf 主要由骨髓中血管周围细胞表达。当 Scf 从造血细胞、成骨细胞、巢蛋白-cre 或巢蛋白-creER 表达细胞中被条件性删除时，HSC 的频率和功能不受影响。然而，当 Scf 从内皮细胞或瘦素受体（Lepr）表达的血管周围基质细胞中被删除时，HSCs 从骨髓中被耗尽。当 Scf 从内皮细胞和 Lepr 表达的血管周围细胞两者中被删除时，大多数 HSCs 被耗尽。因此，HSCs 位于一个血管周围龛位中，其中多种细胞类型表达促进 HSC 维持的因子。
