The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
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 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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Cites
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“…as nonhematopoietic, plastic-adherent, col- ony-forming cells, referred to as colony-forming unit-fibroblasts (CFU-Fs), that can differentiate into osteogenic, chondrogenic, and adipogenic progeny (Bianco et al., 2008; Friedenstein et al., 1970; Horwitz et al., 2005; Pittenger et al., 1999).”
A robust and high-throughput Cre reporting and characterization system for the whole mouse brain
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“Mice All mice were maintained in a C57BL/6 background, including Lepr-cre (DeFalco et al., 2001), Leprfl/fl (Cohen et al., 2001), Ptenfl/fl (Groszer et al., 2001), Scf-GFP (Ding et al., 2012), Cxcl12-DsRed (Ding and Morrison, 2013), Ubc-creER (Ruzankina et al., 2007), Rosa26-CAG-loxp-stop-loxp-tdTomato (Madisen et al.…”
Cytokine-mediated regulation of CXCR4 expression in human neutrophils
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“The expression of Runx2, a transcription factor required for osteogenesis (Komori et al., 1997; Otto et al., 1997), was markedly reduced in LepR+ stromal cells from Lepr-cre; Ptenfl/fl as compared to control mice (Figure 7R).”
A perivascular origin for mesenchymal stem cells in multiple human organs
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“The expression of Runx2, a transcription factor required for osteogenesis (Komori et al., 1997; Otto et al., 1997), was markedly reduced in LepR+ stromal cells from Lepr-cre; Ptenfl/fl as compared to control mice (Figure 7R).”
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“…as nonhematopoietic, plastic-adherent, col- ony-forming cells, referred to as colony-forming unit-fibroblasts (CFU-Fs), that can differentiate into osteogenic, chondrogenic, and adipogenic progeny (Bianco et al., 2008; Friedenstein et al., 1970; Horwitz et al., 2005; Pittenger et al., 1999).”
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“The high expression of Cxcl12 (Figure S1E) and PDGFRa (Figures 1L and 1M) by LepR stromal cells indicates that these cells overlap strongly with CAR cells, which are also found primarily around sinusoids throughout the bone marrow (Omatsu et al., 2010; Sugiyama et al., 2006).”
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Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications
Wang, Y., Chen, X., Cao, W., & Shi, Y. (2014) · Nature Immunology · doi:10.1038/ni.3002 · Cited by 1,452
Adipogenesis and metabolic health
Ghaben, A. L., & Scherer, P. E. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0093-z · Cited by 1,395
Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases
Shi, Y., Wang, Y., Li, Q., Liu, K., Hou, J., Shao, C., & Wang, Y. (2018) · Nature Reviews Nephrology · doi:10.1038/s41581-018-0023-5 · Cited by 1,223
Haematopoietic stem cell activity and interactions with the niche
Pinho, S., & Frenette, P. S. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0103-9 · Cited by 1,064
Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
Cossarizza, A., Chang, H., Radbruch, A., Acs, A., Adam, D., Adam‐Klages, S., Agace, W. W., Aghaeepour, N., Akdiş, M., Allez, M., et al. (2019) · European Journal of Immunology · doi:10.1002/eji.201970107 · Cited by 1,007
Metadata
- 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
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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