Zhou Bo O, Yue Rui, Murphy Malea M, Peyer James G, Morrison Sean J
Children's Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Children's Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute.
Cell Stem Cell. 2014 Aug 7;15(2):154-68. doi: 10.1016/j.stem.2014.06.008. Epub 2014 Jun 19.
Studies of the identity and physiological function of mesenchymal stromal cells (MSCs) have been hampered by a lack of markers that permit both prospective identification and fate mapping in vivo. We found that Leptin Receptor (LepR) is a marker that highly enriches bone marrow MSCs. Approximately 0.3% of bone marrow cells were LepR(+), 10% of which were CFU-Fs, accounting for 94% of bone marrow CFU-Fs. LepR(+) cells formed bone, cartilage, and adipocytes in culture and upon transplantation in vivo. LepR(+) cells were Scf-GFP(+), Cxcl12-DsRed(high), and Nestin-GFP(low), markers which also highly enriched CFU-Fs, but negative for Nestin-CreER and NG2-CreER, markers which were unlikely to be found in CFU-Fs. Fate-mapping showed that LepR(+) cells arose postnatally and gave rise to most bone and adipocytes formed in adult bone marrow, including bone regenerated after irradiation or fracture. LepR(+) cells were quiescent, but they proliferated after injury. Therefore, LepR(+) cells are the major source of bone and adipocytes in adult bone marrow.
间充质基质细胞（MSCs）的身份和生理功能研究一直受到缺乏标记物的阻碍，这些标记物需要能够在体内进行前瞻性鉴定和追踪其命运。我们发现瘦素受体（LepR）是一种能高度富集骨髓间充质干细胞的标记物。约0.3%的骨髓细胞为LepR阳性，其中10%是集落形成单位成纤维细胞（CFU-Fs），占骨髓CFU-Fs的94%。LepR阳性细胞在体外培养和体内移植后可形成骨、软骨和脂肪细胞。LepR阳性细胞为干细胞因子绿色荧光蛋白（Scf-GFP）阳性、趋化因子12红色荧光蛋白（Cxcl12-DsRed）高表达、巢蛋白绿色荧光蛋白（Nestin-GFP）低表达，这些标记物也能高度富集CFU-Fs，但对巢蛋白-雌激素受体（Nestin-CreER）和硫酸软骨素蛋白聚糖2-雌激素受体（NG2-CreER）呈阴性，而CFU-Fs中不太可能发现这些标记物。命运追踪显示，LepR阳性细胞在出生后出现，并产生成年骨髓中形成的大部分骨和脂肪细胞，包括辐射或骨折后再生的骨。LepR阳性细胞处于静止状态，但在损伤后会增殖。因此，LepR阳性细胞是成年骨髓中骨和脂肪细胞的主要来源。
