Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow.
Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow.
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DOI：
10.1016/j.stem.2014.06.008
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发表时间：
2014-08-07
期刊：
影响因子：
23.9
通讯作者：
Morrison, Sean J.
中科院分区：
文献类型：
--
作者：
Zhou, Bo O.;Yue, Rui;Murphy, Malea M.;Peyer, James G.;Morrison, Sean J.
间充质基质细胞（MSC）的身份和生理功能的研究一直受到阻碍，缺乏标记，允许前瞻性的识别和体内的命运映射。我们发现瘦素受体（Leptin Receptor，LepR）是一种高度富集骨髓间充质干细胞的标志物。约0.3%的骨髓细胞为LepR+，其中10%为CFU-F，占骨髓CFU-F的94%。LepR+细胞在培养中和体内移植后形成骨、软骨和脂肪细胞。LepR+细胞是Scf-GFP+、Cxcl 12-DsRedhigh和Nestin-GFP低，这些标记物也高度富集CFU-F，但对Nestin-CreER和NG 2-CreER阴性，这些标记物包括很少的CFU-F。Fate mapping显示LepR+细胞在出生后出现，并在成人骨髓中形成大部分骨和脂肪细胞，包括辐射或骨折后的骨再生。LepR+细胞在损伤后处于静止状态，但增殖。LepR+细胞是成人骨髓中骨和脂肪细胞的主要来源。
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 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-F, accounting for 94% of bone marrow CFU-F. LepR+ cells formed bone, cartilage, and adipocytes in culture and upon transplantation in vivo. LepR+ cells were Scf-GFP+, Cxcl12-DsRedhigh, and Nestin-GFPlow, markers which also highly enriched CFU-F, but negative for Nestin-CreER and NG2-CreER, markers which included few CFU-F. Fate-mapping showed 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 proliferated after injury. LepR+ cells are the major source of bone and adipocytes in adult bone marrow.
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