title: Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow.
abstract: 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.
authors: Children's Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Bo O
authors: BO
authors: Zhou
authors: Children's Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Rui
authors: R
authors: Yue
authors: Children's Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Malea M
authors: MM
authors: Murphy
authors: Children's Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: James G
authors: JG
authors: Peyer
authors: Children's Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute. Electronic address: sean.morrison@utsouthwestern.edu.
authors: Sean J
authors: SJ
authors: Morrison
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D001842:Bone and Bones / Q000378:metabolism*; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000378:metabolism; D010012:Osteogenesis; D054411:Receptors, Leptin / Q000378:metabolism*; D012038:Regeneration; D013234:Stem Cells; D013629:Tamoxifen / Q000737:chemistry; D019076:Transgenes
chemical_list: D020738:Leptin; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; D013629:Tamoxifen; D049452:Green Fluorescent Proteins