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

Bo O. Zhou, Rui Yue, Malea M. Murphy, James G. Peyer, Sean J. Morrison

Research output: Contribution to journalArticlepeer-review

873 Scopus citations


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-DsRedhigh, and Nestin-GFPlow, 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.

Original languageEnglish (US)
Pages (from-to)154-168
Number of pages15
JournalCell Stem Cell
Issue number2
StatePublished - Aug 7 2014

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology


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