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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Multilineage potential of adult human mesenchymal stem cells
Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S., & Marshak, D. R. (1999) · Science · doi:10.1126/science.284.5411.143 · Cited by 21,052 · cited 2×
“…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
Madisen, L., Zwingman, T. A., Sunkin, S. M., Oh, S. W., Zariwala, H. A., Gu, H., Ng, L. L., Palmiter, R. D., Hawrylycz, M. J., Jones, A. R., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2467 · Cited by 6,907 · cited 3×
“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
Nagase, H., Miyamasu, M., Yamaguchi, M., Imanishi, M., Tsuno, N. H., Matsushima, K., Yamamoto, K., Morita, Y., & Hirai, K. (2002) · Journal of Leukocyte Biology · doi:10.1189/jlb.71.4.711 · Cited by 4,713
Komori, T., Yagi, H., Nomura, S., Yamaguchi, A., Sasaki, K., Deguchi, K., Shimizu, Y., Bronson, R. T., Gao, Y.-H., Inada, M., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80258-5 · Cited by 4,244 · cited 2×
“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
Crisan, M., Yap, S., Casteilla, L., Chen, C.-W., Corselli, M., Park, T. S., Andriolo, G., Sun, B., Zheng, B., Zhang, L., et al. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2008.07.003 · Cited by 3,991 · cited 3×
“In vivo, MSCs are often perivascular (Crisan et al., 2008; Sacchetti et al., 2007).”
Mesenchymal and haematopoietic stem cells form a unique bone marrow niche
Méndez‐Ferrer, S., Michurina, T. V., Ferraro, F., Mazloom, A. R., MacArthur, B. D., Lira, S. A., Scadden, D. T., Ma’ayan, A., Enikolopov, G., & Frenette, P. S. (2010) · Nature · doi:10.1038/nature09262 · Cited by 3,381 · cited 9×
“Nestin-CreER-express- ing cells in adult bone marrow can contribute to osteoblasts and chondrocytes, though no quantification was provided regarding their CFU-F content or their level of contribution to new bone (Méndez-Ferrer et al., 2010).”
InfluentialCre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus
Srinivas, S., Watanabe, T., Lin, C.-S., William, C. M., Tanabe, Y., Jessell, T. M., & Costantini, F. (2001) · BMC Developmental Biology · doi:10.1186/1471-213x-1-4 · Cited by 3,121 · cited 3×
“, 2010), Rosa26-loxp-stop-loxp-EYFP (Srinivas et al., 2001), Rosa26-loxp-stop-loxp-iDTR (Buch et al.”
Otto, F., Thornell, A., Crompton, T., Denzel, A., Gilmour, K. C., Rosewell, I. R., Stamp, G., Beddington, R. S. P., Mundlos, S., Olsen, B. R., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80259-7 · Cited by 2,813 · cited 2×
“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).”
Friedenstein, A. J., Chailakhjan, R. K., & Lalykina, K. S. (1970) · Cell Proliferation · doi:10.1111/j.1365-2184.1970.tb00347.x · Cited by 2,724 · cited 2×
“…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).”
Sugiyama, T., Kohara, H., Noda, M., & Nagasawa, T. (2006) · Immunity · doi:10.1016/j.immuni.2006.10.016 · Cited by 2,419 · cited 2×
“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).”
Flagged first, then by citations
Cited by
Sorted by citations
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
The bone marrow microenvironment at single-cell resolution
Tikhonova, A. N., Dolgalev, I., Hu, H., Sivaraj, K. K., Hoxha, E., Cuesta-Domínguez, Á., Pinho, S., Akhmetzyanova, I., Gao, J., Witkowski, M., et al. (2019) · Nature · doi:10.1038/s41586-019-1104-8 · Cited by 936
A Cellular Taxonomy of the Bone Marrow Stroma in Homeostasis and Leukemia
Baryawno, N., Przybylski, D., Kowalczyk, M. S., Kfoury, Y. S., Sévère, N., Gustafsson, K. U., Kokkaliaris, K. D., Mercier, F., Tabaka, M., Hofree, M., et al. (2019) · Cell · doi:10.1016/j.cell.2019.04.040 · Cited by 916
Baccin, C., Al-Sabah, J., Velten, L., Helbling, P. M., Grünschläger, F., Hernández-Malmierca, P., Nombela‐Arrieta, C., Steinmetz, L. M., Trumpp, A., & Haas, S. F. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0439-6 · Cited by 894
Ambrosi, T. H., Scialdone, A., Graja, A., Gohlke, S., Jank, A.-M., Bocian, C., Woelk, L., Fan, H., Logan, D. W., Schürmann, A., et al. (2017) · Cell Stem Cell · doi:10.1016/j.stem.2017.02.009 · Cited by 856
“In support of this observation, clonal analysis of PaS or LepR+ cells showed multipotency only in a smaller subset of clones that may have derived from sub-populations expressing CD24 (Morikawa et al., 2009a; Zhou et al., 2014).”
BackgroundResultInfluentialHematopoietic stem cell niche maintenance during homeostasis and regeneration
Mendelson, A., & Frenette, P. S. (2014) · Nature Medicine · doi:10.1038/nm.3647 · Cited by 819
Osteoimmunology: evolving concepts in bone–immune interactions in health and disease
Tsukasaki, M., & Takayanagi, H. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0178-8 · Cited by 812
Identification and Specification of the Mouse Skeletal Stem Cell
Chan, C. K. F., Seo, E. Y., Chen, J. Y., Lo, D. D., McArdle, A., Sinha, R., Tevlin, R., Seita, J., Vincent-Tompkins, J., Wearda, T. L., et al. (2015) · Cell · doi:10.1016/j.cell.2014.12.002 · Cited by 763
“…consists of eight different cellular subpopulations with distinct skeletogenic properties and encompasses subpopulations that have characteristics of described skeletogenic cell types identified by lineage tracing (Bianco, 2014, Méndez-Ferrer et al., 2010; Park et al., 2012; Zhou et al., 2014).”
Samsonraj, R. M., Raghunath, M., Nurcombe, V., Hui, J. H. P., van Wijnen, A. J., & Cool, S. M. (2017) · Stem Cells Translational Medicine · doi:10.1002/sctm.17-0129 · Cited by 732
Adult haematopoietic stem cell niches
Crane, G. M., Jeffery, E., & Morrison, S. J. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.53 · Cited by 712
Self-citationDeep imaging of bone marrow shows non-dividing stem cells are mainly perisinusoidal
Acar, M., Kocherlakota, K. S., Murphy, M. M., Peyer, J. G., Oguro, H., Inra, C. N., Jaiyeola, C., Zhao, Z., Luby‐Phelps, K., & Morrison, S. J. (2015) · Nature · doi:10.1038/nature15250 · Cited by 729
Self-citationDiscovery of a periosteal stem cell mediating intramembranous bone formation
Debnath, S., Yallowitz, A. R., McCormick, J., Lalani, S., Zhang, T., Xu, R., Li, N., Liu, Y., Yang, Y. S., Eiseman, M., et al. (2018) · Nature · doi:10.1038/s41586-018-0554-8 · Cited by 700
The genetics of myelodysplastic syndrome: from clonal haematopoiesis to secondary leukaemia
Sperling, A. S., Gibson, C. J., & Ebert, B. L. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.112 · Cited by 695
“HSCs exist within a supportive stromal microenvironment comprised of sinusoidal vascular endothelial cells, osteoblasts, adipocyts, and other components, which can also alter HSC function and differentiation 182–184 .”
Gremlin 1 Identifies a Skeletal Stem Cell with Bone, Cartilage, and Reticular Stromal Potential
Worthley, D. L., Churchill, M., Compton, J. T., Tailor, Y. H., Rao, M., Si, Y., Levin, D. E., Schwartz, M. G., Uygur, A., Hayakawa, Y., et al. (2015) · Cell · doi:10.1016/j.cell.2014.11.042 · Cited by 645
“Recently, perisinusoidal mesenchymal cells expressing Lepr were found to include multipotent, colony-forming unit-fibroblasts (CFU-Fs) (Zhou et al., 2014).”
BackgroundMethodInfluentialIdentification of the Human Skeletal Stem Cell
Chan, C. K. F., Gulati, G. S., Sinha, R., Vincent-Tompkins, J., Lopez, M., Carter, A. C., Ransom, R. C., Reinisch, A., Wearda, T. L., Murphy, M. P., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.029 · Cited by 615
“Similarly, a significant amount of effort has been devoted toward identifying the cellular origins of the non-hematopoietic lineages in skeletal tissue, such as bone, cartilage, vascular endothelium, and stroma (Chan et al., 2015b; Marecic et al., 2015; Méndez-Ferrer et al., 2010; Worthley et al., 2015; Zhou et al., 2…”
BackgroundSelf-citationCellular biology of fracture healing
Bahney, C. S., Zondervan, R. L., Allison, P., Theologis, A., Ashley, J. W., Ahn, J., Miclau, T., Marcucio, R. S., & Hankenson, K. D. (2019) · Journal of Orthopaedic Research · doi:10.1002/jor.24170 · Cited by 577
“Gremlin-CreERT2 and LepR-Cre cells have also been shown to give rise to osteoblasts and chondrocytes in the fracture callus.(100,101) Table S2 provides a summary of recent investigations in bone healing that employed Cre systems and includes additional Cre mice relevant to fracture biology that have yet to be studied.”
Han, Y., You, X., Xing, W., Zhang, Z., & Zou, W. (2018) · Bone Research · doi:10.1038/s41413-018-0019-6 · Cited by 598
Identification of senescent cells in the bone microenvironment
Farr, J. N., Fraser, D. G., Wang, H., Jaehn, K., Ogrodnik, M. B., Weivoda, M. M., Drake, M. T., Tchkonia, T., LeBrasseur, N. K., Kirkland, J. L., et al. (2016) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2892 · Cited by 562
“As noted earlier, the Morrison laboratory recently showed that bone marrow Lin–/Leprþ cells are the main source of bone formed by bone marrow–derived osteoblast progenitors.((27))”
Influentialde Lageneste, O. D., Julien, A., Abou-Khalil, R., Frangi, G., Carvalho, C., Cagnard, N., Cordier, C., Conway, S. J., & Colnot, C. (2018) · Nature Communications · doi:10.1038/s41467-018-03124-z · Cited by 573
Mesenchymal Cell Contributions to the Stem Cell Niche
Kfoury, Y. S., & Scadden, D. T. (2015) · Cell stem cell · doi:10.1016/j.stem.2015.02.019 · Cited by 558
Guidelines for the use of flow cytometry and cell sorting in immunological studies *
Cossarizza, A., Chang, H., Radbruch, A., Akdiş, M., Andrä, I., Annunziato, F., Bächer, P., Barnaba, V., Battistini, L., Bauer, W. M., et al. (2017) · European Journal of Immunology · doi:10.1002/eji.201646632 · Cited by 595
Anatomical, Physiological, and Functional Diversity of Adipose Tissue
Zwick, R. K., Guerrero‐Juarez, C. F., Horsley, V., & Plikus, M. V. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.12.002 · Cited by 562
“Following radiation injury, these progenitors can also contribute to adipocytes. bmAT progenitors can also be marked using Lepr-Cre (Zhou et al., 2014); however, their lineage relationship with Osterix+ mesenchymal progenitors remains unclear.”
InfluentialBone marrow adipocytes promote the regeneration of stem cells and hematopoiesis by secreting SCF
Zhou, B., Yu, H., Yue, R., Zhao, Z.-Y., Rios, J., Naveiras, O., & Morrison, S. (2017) · Nature Cell Biology · doi:10.1038/ncb3570 · Cited by 466
Self-citationGuidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)
Cossarizza, A., Chang, H., Radbruch, A., Abrignani, S., Addo, R., Akdis, M., Andrä, I., Andreata, F., Annunziato, F., Arranz, E., et al. (2021) · European Journal of Immunology · doi:10.1002/eji.202170126 · Cited by 531
Yue, R., Zhou, B. O., Shimada, I. S., Zhao, Z., & Morrison, S. J. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.02.015 · Cited by 495
“These cells also express LepR: LepR+ cells include nearly all of the CFU-F in adult mouse bone marrow (Zhou et al., 2014).”
InfluentialSelf-citationBone remodeling: an operational process ensuring survival and bone mechanical competence
Bolamperti, S., Villa, I., & Rubinacci, A. (2022) · Bone Research · doi:10.1038/s41413-022-00219-8 · Cited by 482
Tumour-associated mesenchymal stem/stromal cells: emerging therapeutic targets
Shi, Y., Du, L., Lin, L., & Wang, Y. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.193 · Cited by 463
Lin, H., Sohn, J., Shen, H., Langhans, M. T., & Tuan, R. S. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.06.026 · Cited by 454
“LepR positive cells were shown to be capable of giving rise to osteoblasts and adipocytes in bone marrow [25].”
BackgroundBlood vessel formation and function in bone
Sivaraj, K. K., & Adams, R. H. (2016) · Development · doi:10.1242/dev.136861 · Cited by 454
“These cells, which show low expression of the nestin-GFP reporter, have the capability to differentiate to different mesenchymal lineage cells, such as bone, cartilage and adipocytes (Zhou et al., 2014).”
BackgroundMaking sense of hematopoietic stem cell niches
Boulais, P. E., & Frenette, P. S. (2015) · Blood · doi:10.1182/blood-2014-09-570192 · Cited by 469
“Nes-GFP(1) LepR(1) stromal cells indeed appear to contain MSPC activity in the adult bone marrow.(85,86) The observation that Osx, which is a transcription factor thought to be specific for the osteolineage, marks the stroma during development was independently reported by other groups.”
BackgroundWu, Y., Xie, L., Wang, M., Xiong, Q., Guo, Y., Liang, Y., Li, J., Sheng, R., Deng, P., Wang, Y., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06898-4 · Cited by 432
“Cells were cultured in six-well plates and stimulated with vehicle or 100 nM human recombinant PTH (1-34) (Bachem, Torrance, CA, USA) at 37 °C for 15 min67.”
BackgroundMethodInfluentialMesenchymal stem cells in fibrotic disease
El Agha, E., Kramann, R., Schneider, R. K., Li, X., Seeger, W., Humphreys, B. D., & Bellusci, S. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.07.011 · Cited by 430
Differential cytokine contributions of perivascular haematopoietic stem cell niches
Asada, N., Kunisaki, Y., Pierce, H., Wang, Z., Fernandez, N., Birbrair, A., Ma’ayan, A., & Frenette, P. S. (2017) · Nature Cell Biology · doi:10.1038/ncb3475 · Cited by 453
The suture provides a niche for mesenchymal stem cells of craniofacial bones
Zhao, H., Feng, J., Ho, T., Grimes, W., Urata, M. M., & Chai, Y. (2015) · Nature Cell Biology · doi:10.1038/ncb3139 · Cited by 429
Normal and Leukemic Stem Cell Niches: Insights and Therapeutic Opportunities
Schepers, K., Campbell, T., & Passegue, E. A. (2015) · Cell stem cell · doi:10.1016/j.stem.2015.02.014 · Cited by 431
“CAR, CXCL12bright MSCs; E-Sel, E-selectin; LEP-R, NG2 LEPR+Nesbright MSCs; NG2, NG2+LEP-R Nesdim MSCs; nmSC, non-myelinating Schwann cells; NorE, norepinephrine; OCL, osteoclasts; OPr, osteoprogenitors; OsM, osteomacs.”
InfluentialA subset of chondrogenic cells provides early mesenchymal progenitors in growing bones
Ono, N., Ono, W., Nagasawa, T., & Kronenberg, H. M. (2014) · Nature Cell Biology · doi:10.1038/ncb3067 · Cited by 418
Osteoporosis and periodontal diseases – An update on their association and mechanistic links
Yu, B., & Wang, C. (2022) · Periodontology 2000 · doi:10.1111/prd.12422 · Cited by 437
Bianco, P., & Robey, P. G. (2015) · Development · doi:10.1242/dev.102210 · Cited by 402
Tissue clearing of both hard and soft tissue organs with the PEGASOS method
Jing, D., Zhang, S., Luo, W., Gao, X., Men, Y., Ma, C., Liu, X., Yi, Y., Bugde, A., Zhou, B. O., et al. (2018) · Cell Research · doi:10.1038/s41422-018-0049-z · Cited by 400
Self-citationNestin-expressing progenitor cells: function, identity and therapeutic implications
Bernal, A., & Arranz, L. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2794-z · Cited by 415
“This may underlie controversial findings like presence of recombination in fully differentiated neurons [59] or their poor colony forming unit fibroblastic activity in adult bone marrow [60].”
BackgroundNiches for Hematopoietic Stem Cells and Their Progeny
Wei, Q., & Frenette, P. S. (2018) · Immunity · doi:10.1016/j.immuni.2018.03.024 · Cited by 398
“Later, an Scf.-GFP knockin reporter also identified a Leptin receptor-expressing (LEPR+) cell population with a similar perivascular distribution and mesenchymal potential (Zhou et al., 2014, Mizoguchi et al., 2014, Ding et al., 2012).”
Gli1 identifies osteogenic progenitors for bone formation and fracture repair
Shi, Y., He, G., Lee, W., McKenzie, J. A., Silva, M. J., & Long, F. (2017) · Nature Communications · doi:10.1038/s41467-017-02171-2 · Cited by 345
Zhong, L., Yao, L., Tower, R. J., Wei, Y., Miao, Z., Park, J., Shrestha, R., Wang, L., Yu, W. H., Holdreith, N., et al. (2020) · eLife · doi:10.7554/elife.54695 · Cited by 345
“Based on previous studies that leptin receptor (Lepr) marks adult bone marrow MSCs (Zhou et al., 2014) and Lepr cells serve as niche for hematopoietic progenitors (Comazzetto et al.”
BackgroundMethodInfluentialReciprocal regulation of mesenchymal stem cells and immune responses
Wang, Y., Fang, J., Liu, B., Shao, C., & Shi, Y. (2022) · Cell stem cell · doi:10.1016/j.stem.2022.10.001 · Cited by 336
Sharpe, P. T. (2016) · Development · doi:10.1242/dev.134189 · Cited by 310
“Other genetic lineage-tracing experiments have identified populations of leptin receptor (LepR)- and gremlin 1-positive cells that give rise to a range of skeletal cell types in vivo (Worthley et al., 2015; Zhou et al., 2014).”
BackgroundA mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis
Shen, B., Tasdogan, A., Ubellacker, J. M., Zhang, J., Nosyreva, E. D., Du, L., Murphy, M. M., Hu, S., Yi, Y., Kara, N., et al. (2021) · Nature · doi:10.1038/s41586-021-03298-5 · Cited by 310
Self-citationMatsushita, Y., Nagata, M., Kozloff, K. M., Welch, J. D., Mizuhashi, K., Tokavanich, N., Hallett, S. A., Link, D. C., Nagasawa, T., Ono, W., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-14029-w · Cited by 305
Niches that regulate stem cells and hematopoiesis in adult bone marrow
Comazzetto, S., Shen, B., & Morrison, S. J. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.05.018 · Cited by 312
Self-citationGomes, A. C., Hara, T., Lim, V., Herndler‐Brandstetter, D., Nevius, E., Sugiyama, T., Tani‐ichi, S., Schlenner, S., Richie, E. R., Rodewald, H.-R., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.11.004 · Cited by 288
“CAR cells share functional similarities with a subset of mesenchymal progenitor cells that expresses Leptin receptor (Omatsu et al., 2010; Zhou et al., 2014).”
Frodermann, V., Rohde, D., Courties, G., Severe, N., Schloss, M. J., Amatullah, H., McAlpine, C. S., Cremer, S., Hoyer, F. F., Ji, F., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0633-x · Cited by 292
Aghajanian, P., & Mohan, S. (2018) · Bone Research · doi:10.1038/s41413-018-0021-z · Cited by 288
“In this study, the authors speculate that the early mesenchymal progenitors expressing chondrocyte markers provide a rapid source of osteoblasts during the rapid phase of bone growth, but are different from adult mesenchymal progenitors.(48) The dedifferentiation to redifferentiation model provides an alternate view o…”
BackgroundNiche heterogeneity in the bone marrow
Birbrair, A., & Frenette, P. S. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13016 · Cited by 313
Advancing application of mesenchymal stem cell-based bone tissue regeneration
Shang, F., Yu, Y., Liu, S., Ming, L., Zhang, Y., Zhou, Z., Zhao, J., & Jin, Y. J. (2020) · Bioactive Materials · doi:10.1016/j.bioactmat.2020.08.014 · Cited by 293
“Currently, the putative contributions to skeletal homeostasis have made MSCs the focus of extensive investigations worldwide to elucidate pathogenesis of bone diseases [66,67].”
BackgroundLi, J., Chen, X., Lu, L., & Yu, X. (2020) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2020.02.003 · Cited by 278
A perisinusoidal niche for extramedullary haematopoiesis in the spleen
Inra, C. N., Zhou, B. O., Acar, M., Murphy, M. M., Richardson, J. A., Zhao, Z., & Morrison, S. J. (2015) · Nature · doi:10.1038/nature15530 · Cited by 282
Self-citationNeural Regulation of Hematopoiesis, Inflammation, and Cancer
Hanoun, M., Maryanovich, M., Arnal-Estapé, A., & Frenette, P. S. (2015) · Neuron · doi:10.1016/j.neuron.2015.01.026 · Cited by 265
Glutamine Metabolism Regulates Proliferation and Lineage Allocation in Skeletal Stem Cells
Yu, Y., Newman, H., Shen, L., Sharma, D., Hu, G., Mirando, A. J., Zhang, H., Knudsen, E., Zhang, G.-F., Hilton, M. J., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.01.016 · Cited by 253
Mesenchymal stromal cells: Putative microenvironmental modulators become cell therapy
Krampera, M., & Blanc, K. L. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.09.006 · Cited by 273
Stem cells of the suture mesenchyme in craniofacial bone development, repair and regeneration
Maruyama, T., Jeong, J., Sheu, T., & Hsu, W. (2016) · Nature Communications · doi:10.1038/ncomms10526 · Cited by 258
The mesenchymal context in inflammation, immunity and cancer
Koliaraki, V., Prados, A., Armaka, M., & Kollias, G. A. (2020) · Nature Immunology · doi:10.1038/s41590-020-0741-2 · Cited by 252
CXCL12-Producing Vascular Endothelial Niches Control Acute T Cell Leukemia Maintenance
Pitt, L. A., Tikhonova, A. N., Hu, H., Trimarchi, T., King, B., Gong, Y., Sánchez-Martín, M., Tsirigos, A., Littman, D. R., Ferrando, A. A., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.05.002 · Cited by 252
“To label perivascular cells, Lepr-cre trangenic mice were crossed to LoxP-tdTomato mice (Lepr-cre; LoxP-tdTomato) (Figures S2Ae and S2Af), as it was previously demonstrated that Leprin receptor is highly expressed in perivascular stromal cells (Zhou et al., 2014).”
BackgroundSelf-citationAlpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations
Wang, Y., Deng, P., Liu, Y., Wu, Y., Chen, Y., Guo, Y., Zhang, S., Zheng, X., Zhou, L., Liu, W., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19360-1 · Cited by 261
Autophagy in bone homeostasis and the onset of osteoporosis
Yin, X., Zhou, C., Li, J., Liu, R., Shi, B., Yuan, Q., & Zou, S. (2019) · Bone Research · doi:10.1038/s41413-019-0058-7 · Cited by 235
Regulation of Bone Remodeling by Parathyroid HormonePreprint
Wein, M. N., & Kronenberg, H. M. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a031237 · Cited by 257
“A different pattern of expression was revealed through the use the leptin receptor-Cre transgene to mark mesenchymal cells in bone (Zhou et al. 2014).”
BackgroundInhibition of overactive TGF-β attenuates progression of heterotopic ossification in mice
Wang, X., Li, F., Xie, L., Crane, J. L., Zhen, G., Mishina, Y. M., Deng, R., Gao, B., Chen, H., Liu, S., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-02988-5 · Cited by 247
Advances in stem cell research and therapeutic development
Luca, M. D., Aiuti, A., Cossu, G., Parmar, M., Pellegrini, G., & Robey, P. G. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0344-z · Cited by 240
Long noncoding RNA Bmncr regulates mesenchymal stem cell fate during skeletal aging
Li, C., Xiao, Y., Yang, M., Su, T., Sun, X. H., Guo, Q., Huang, Y., & Luo, X. (2018) · Journal of Clinical Investigation · doi:10.1172/jci99044 · Cited by 235
Yang, L., He, Y.-T., Dong, S., Wei, X., Chen, Z., Zhang, B., Chen, W., Yang, X., Wang, F., Shang, X.-M., et al. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-003534 · Cited by 234
“Moreover, CSF1 was also found to be highly expressed by mast cells, indicating that mast cells might play an important role in regulating the migration, proliferation, and function of macrophages in the TME.”
Jeffery, E. C., Mann, T. L. A., Pool, J. A., Zhao, Z., & Morrison, S. J. (2022) · Cell stem cell · doi:10.1016/j.stem.2022.10.002 · Cited by 241
Self-citationMapping Distinct Bone Marrow Niche Populations and Their Differentiation Paths
Wolock, S. L., Krishnan, I., Tenen, D. E., Matkins, V. R., Camacho, V., Patel, S. B., Agarwal, P., Bhatia, R., Tenen, D. G., Klein, A. M., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.06.031 · Cited by 240
“Meanwhile, ablation studies have shown that MSC populations expressing Nestin, Cxcl12, stem cell factor (SCF), and Leptin receptor are essential for supporting blood cell maintenance and differentiation (Dar et al., 2005; Ding and Morrison, 2013; Ding et al., 2012; Méndez-Ferrer et al., 2010; Omatsu et al., 2010; Zhou…”
The hematopoietic stem cell niche in homeostasis and disease
Calvi, L. M., & Link, D. C. (2015) · Blood · doi:10.1182/blood-2015-07-533588 · Cited by 238
Single-cell RNA landscape of the osteoimmunology microenvironment in periodontitis
Chen, Y., Wang, H., Yang, Q., Zhao, W., Chen, Y., Ni, Q., Li, W., Shi, J., Zhang, W., Li, L., et al. (2022) · Theranostics · doi:10.7150/thno.65694 · Cited by 233
“We also confirmed the expression of CD55+LepR+ MSCs by immunofluorescence staining using periodontal tissues from HC and PD samples.”
BackgroundInfluentialThe hematologic consequences of obesity
Purdy, J. C., & Shatzel, J. J. (2021) · European Journal Of Haematology · doi:10.1111/ejh.13560 · Cited by 227
“Zhou et al (2014)55 have shown that bone marrow mesenchymal stromal cells are leptin receptor positive and although these are defined as non-hematopoietic, as they rather differentiate into osteogenic, chondrogenic, and adipogenic progeny, they do give rise to bony ossicles that become invested…”
BackgroundSpecification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts
Kumar, A., D'Souza, S. S., Moskvin, O. V., Toh, H., Wang, B., Zhang, J., Swanson, S. A., Guo, L., Thomson, J. A., & Slukvin, I. I. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.05.019 · Cited by 220
“Next, we analyzed whether MB colonies expressed genes known to be present in mouse and human primitive bone marrow mesenchymal progenitors, including Prrx1 (Greenbaum et al., 2013), Nes (Méndez-Ferrer et al., 2010), Lepr (Ding et al., 2012; Zhou et al., 2014), Cxcl12 (Ding and Morrison, 2013), Sp7 (Liu et al., 2013),…”
Establishing Criteria for Human Mesenchymal Stem Cell Potency
Samsonraj, R. M., Rai, B., Sathiyanathan, P., Puan, K. J., Rötzschke, O., Hui, J. H. P., Raghunath, M., Stanton, L. W., Nurcombe, V., & Cool, S. M. (2015) · Stem Cells · doi:10.1002/stem.1982 · Cited by 221
Mitchell, C. A., Verovskaya, E. V., Calero‐Nieto, F. J., Olson, O. C., Swann, J. W., Wang, X., Hérault, A., Dellorusso, P. V., Zhang, S. Y., Svendsen, A. F., et al. (2023) · Nature Cell Biology · doi:10.1038/s41556-022-01053-0 · Cited by 224
Scott, R. W., Arostegui, M., Schweitzer, R., Rossi, F. M. V., & Underhill, T. M. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.11.004 · Cited by 214
“Mesenchymal populations within various tissues have been identified using a variety of markers including Nestin-GFP, Gli1, Grem1, Lepr, PDGFRA, Sca1 (LY6A) and CD34, and combinations thereof (Joe et al., 2010; Kramann et al., 2015; Mendez-Ferrer et al., 2010; Uezumi et al., 2010; Worthley et al., 2015; Zhou et al., 20…”
BackgroundThe Origin and Contribution of Cancer-Associated Fibroblasts in Colorectal Carcinogenesis
Kobayashi, H., Gieniec, K. A., Lannagan, T. R. M., Wang, T., Asai, N., Mizutani, Y., Iida, T., Ando, R., Thomas, E. M., Sakai, A., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.11.037 · Cited by 214
Tang, Y., Feinberg, T. Y., Keller, E. T., Li, X.-Y., & Weiss, S. J. (2016) · Nature Cell Biology · doi:10.1038/ncb3394 · Cited by 208
Age-related inflammation triggers skeletal stem/progenitor cell dysfunction
Josephson, A. M., Bradaschia-Corrêa, V., Lee, S., Leclerc, K., Patel, K. S., Muiños-López, E., Litwa, H. P., Neibart, S. S., Kadiyala, M. L., Wong, M. Z., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1810692116 · Cited by 210
“To determine whether a decline in SSPC number is responsible for the impaired regenerative capacity of the aging skeleton, as seen in our human cohort, we used FACS with the inclusive SSPC marker LepR (12).”
BackgroundMethodInfluentialExosome-guided bone targeted delivery of Antagomir-188 as an anabolic therapy for bone loss
Hu, Y., Li, X., Zhang, Q., Gu, Z., Luo, Y., Guo, J., Wang, X., Jing, Y., Chen, X., & Su, J. (2021) · Bioactive Materials · doi:10.1016/j.bioactmat.2021.02.014 · Cited by 215
“Bone marrow mesenchymal stem cells (BMSCs), the progenitors of bone marrow adipocytes and osteoblasts, constitute niches of hematopoiesis in the bone marrow [1].”
BackgroundMarrow Adipose Tissue: Trimming the Fat
Scheller, E. L., Cawthorn, W. P., Burr, A. A., Horowitz, M. C., & MacDougald, O. A. (2016) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2016.03.016 · Cited by 202
Quiescent Bone Lining Cells Are a Major Source of Osteoblasts During Adulthood
Matic, I., Matthews, B. G., Wang, X., Dyment, N. A., Worthley, D. L., Rowe, D. W., Grcevic, D., & Kalajzic, I. (2016) · Stem Cells · doi:10.1002/stem.2474 · Cited by 195
Luo, Y., Chen, G., Hannemann, N., Ipseiz, N., Krönke, G., Bäuerle, T., Munos, L., Wirtz, S. J., Schett, G. A., & Bözec, A. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.08.020 · Cited by 201
“In addition, the increased adipocyte differentiation in BM of HFD mice was associated with an enhanced expression of PPARg affecting the balance of MSC differentiation into adipocyte (Ding et al., 2012; Duque et al., 2013; Wan, 2010; Zhou et al., 2014).”
BackgroundA Revised Perspective of Skeletal Stem Cell Biology
Ambrosi, T. H., Longaker, M. T., & Chan, C. K. F. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00189 · Cited by 196
Yu, B., Huo, L., Liu, Y., Deng, P., Szymanski, J. M., Li, J., Luo, X., Hong, C., Lin, J. D., & Wang, C. (2018) · Cell stem cell · doi:10.1016/j.stem.2018.06.009 · Cited by 196
Comazzetto, S., Murphy, M. M., Berto, S., Jeffery, E. C., Zhao, Z., & Morrison, S. J. (2019) · Cell stem cell · doi:10.1016/j.stem.2018.11.022 · Cited by 206
“3% of young adult bone marrow cells (Ding et al., 2012; Zhou et al., 2014).”
BackgroundSelf-citationZhou, B. O., Ding, L., & Morrison, S. J. (2015) · eLife · doi:10.7554/elife.05521 · Cited by 188
“Consistent with the conclusion that HSC niche cells include mesenchymal stem/stromal cells (Sacchetti et al., 2007; Mendez-Ferrer et al., 2010), the LepR+ cells are highly enriched for CFU-F and give rise to most of the osteoblasts and fat cells that form in adult bone marrow (Zhou et al., 2014).”
BackgroundResultInfluentialSelf-citationHorowitz, M., Berry, R., Holtrup, B., Sebo, Z. L., Nelson, T., Fretz, J. A., Lindskog, D., Kaplan, J. L., Ables, G., Rodeheffer, M. S., et al. (2017) · Adipocyte · doi:10.1080/21623945.2017.1367881 · Cited by 172
“This is because it appears early in postnatal development, is in high concentration in this site compared with rMAT and does not appear to be susceptible to agents that induce rMAT.”
BackgroundInfluentialIdentification of Functionally Distinct Mx1+αSMA+ Periosteal Skeletal Stem Cells
Ortinau, L. C., Wang, H., Lei, K., Deveza, L. R., Jeong, Y., Hara, Y., Grafe, I., Rosenfeld, S. B., Lee, D., Lee, B., et al. (2019) · Cell stem cell · doi:10.1016/j.stem.2019.11.003 · Cited by 190
“BM-SSCs labeled by LepR (Zhou et al., 2014) or Grem1 (Worthley et al.”
BackgroundMethodInfluentialJoint morphogenetic cells in the adult mammalian synovium
Roelofs, A. J., Zupan, J., Riemen, A. H. K., Kania, K., Ansboro, S., White, N., Clark, S. M., & Bari, C. D. (2017) · Nature Communications · doi:10.1038/ncomms15040 · Cited by 187
Gao, B., Deng, R., Chai, Y., Chen, H. H., Hu, B., Wang, X., Zhu, S., Cao, Y. B., Ni, S., Wan, M., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci98857 · Cited by 184
FOXP1 controls mesenchymal stem cell commitment and senescence during skeletal aging
Li, H., Liu, P., Xu, S., Li, Y., Dekker, J. D., Li, B., Fan, Y., Zhang, Z., Hong, Y., Yang, G., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci89511 · Cited by 180
Isolation and characterization of primary bone marrow mesenchymal stromal cells
Li, H., Ghazanfari, R., Zacharaki, D., Lim, H. C., & Scheding, S. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13102 · Cited by 180
Tracing the skeletal progenitor transition during postnatal bone formation
Shu, H. S., Liu, Y. L., Tang, X. T., Zhang, X. S., Zhou, B., Zou, W., & Zhou, B. O. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.08.010 · Cited by 177
Self-citationStem cell-based bone regeneration in diseased microenvironments: Challenges and solutions
Sui, B., Hu, C., Liu, A., Zheng, C., Xuan, K., & Jin, Y. J. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.10.046 · Cited by 173
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
