Institute of Physiology I, Life&Brain Center, Medical Faculty, University of Bonn, 53105 Bonn, Germany.
Institute of Physiology I, Life&Brain Center, Medical Faculty, University of Bonn, 53105 Bonn, Germany; Department of Cardiac Surgery, Medical Faculty, University of Bonn, 53105 Bonn, Germany; Department of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Cell Stem Cell. 2018 Feb 1;22(2):262-276.e7. doi: 10.1016/j.stem.2018.01.008.
Despite much work studying ex vivo multipotent stromal cells (MSCs), the identity and characteristics of MSCs in vivo are not well defined. Here, we generated a CD73-EGFP reporter mouse to address these questions and found EGFP MSCs in various organs. In vivo, EGFP mesenchymal cells were observed in fetal and adult bones at proliferative ossification sites, while in solid organs EGFP cells exhibited a perivascular distribution pattern. EGFP cells from the bone compartment could be clonally expanded ex vivo from single cells and displayed trilineage differentiation potential. Moreover, in the central bone marrow CD73-EGFP specifically labeled sinusoidal endothelial cells, thought to be a critical component of the hematopoietic stem cell niche. Purification and molecular characterization of this CD73-EGFP population revealed an endothelial subtype that also displays a mesenchymal signature, highlighting endothelial cell heterogeneity in the marrow. Thus, the CD73-EGFP mouse is a powerful tool for studying MSCs and sinusoidal endothelium.
尽管已经进行了大量研究多能基质细胞（MSCs）的体外实验，但体内 MSC 的特性和特征尚未得到很好的定义。在这里，我们构建了一个 CD73-EGFP 报告基因小鼠来解决这些问题，并在各种器官中发现了 EGFP-MSCs。在体内，EGFP 间充质细胞存在于胎儿和成年骨的增殖性成骨部位，而在实体器官中，EGFP 细胞表现出血管周围的分布模式。来自骨腔室的 EGFP 细胞可从单个细胞中进行体外克隆扩增，并表现出三系分化潜能。此外，在中央骨髓中，CD73-EGFP 特异性标记窦状内皮细胞，这些细胞被认为是造血干细胞龛的关键组成部分。对该 CD73-EGFP 群体的纯化和分子特征分析揭示了一种内皮亚型，也显示出间充质特征，突出了骨髓中内皮细胞的异质性。因此，CD73-EGFP 小鼠是研究 MSCs 和窦状内皮细胞的有力工具。
