Leptin-Receptor-Expressing Mesenchymal Stromal Cells Represent the Main Source of Bone Formed by Adult Bone Marrow
Open accessAbstract
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.
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Type H vessels respond to intermittent anabolic PTH, which promotes detachment of LepR+ pericytes from CD31hi/Edmhi vessels.
“Type H vessels respond to the administration of intermittent anabolic PTH (iPTH), which promotes the detachment of leptin receptor-expressing (LepR+) cells, which are pericytes that can differentiate into osteoprogenitors,134 from CD31hi/Edmhi vessels.”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [134]
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- Authors
- Zhou, B. O., Yue, R., Murphy, M. M., Peyer, J. G., & Morrison, S. J.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Morrison, Sean J.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 15
- Issue
- 2
- Pages
- 154-168
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC4127103
- OpenAlex
- W2078719918
- Cited by
- 1,381
- References
- 53
- Citations by year
- 2026: 84 · 2025: 92 · 2024: 133 · 2023: 153 · 2022: 148 · 2021: 147 · 2020: 153 · 2019: 114 · 2018: 99 · 2017: 87 · 2016: 89 · 2015: 66 · 2014: 12 · 2013: 2
- FWCI
- 42.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Heart, Lung, and Blood Institute (HL097760, R01HL097760)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- mesenchymal stem cells, leptin receptor, bone marrow, bone formation, adipogenesis, chondrogenesis, CFU-F, fate mapping, cell markers, fracture healing, quiescent cells, stem cell proliferation
- MeSH terms
- Animals, Bone and Bones, Bone Marrow, Bone Marrow Cells, Flow Cytometry, Male, Mice, Inbred C57BL, Osteoblasts, Osteogenesis, Regeneration, Stem Cells, Tamoxifen, Adipocytes, Transgenes, Chondrocytes, Leptin, Cell Proliferation, Green Fluorescent Proteins, Mice, Receptors, Leptin, Mesenchymal Stem Cells
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