Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / metabolism
  • Animals
  • Bone Marrow / metabolism
  • Bone Marrow Cells / cytology
  • Bone and Bones / metabolism*
  • Cell Proliferation
  • Chondrocytes / cytology
  • Chondrocytes / metabolism
  • Flow Cytometry
  • Green Fluorescent Proteins / metabolism
  • Leptin / metabolism
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Osteoblasts / metabolism
  • Osteogenesis
  • Receptors, Leptin / metabolism*
  • Regeneration
  • Stem Cells
  • Tamoxifen / chemistry
  • Transgenes


  • Leptin
  • Receptors, Leptin
  • leptin receptor, mouse
  • Tamoxifen
  • Green Fluorescent Proteins