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).”
Cited by
Sorted by citations
Items 601–700 of 1,001
Sarkaria, S. M., Decker, M., & Ding, L. (2018) · BioEssays · doi:10.1002/bies.201700190 · Cited by 22
Zhu, F., Ji, L., Dai, K., Deng, S., Wang, J., & Liu, C. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2410579121 · Cited by 24
“Leptin Receptor (LepR) and Pdgfr α (CD140 α ) are markers highly enriched in BMSCs ( 35 , 36 ).”
Ngo, H. X., Dong, Q. N., Bai, Y., Sha, J., Ishizuka, S., Okui, T., Sukegawa, S., & Kanno, T. (2020) · Nanomaterials · doi:10.3390/nano11010022 · Cited by 21
“LepR-positive cells are normally quiescent, but proliferate after an injury to regenerate bone [35].”
BackgroundJejunal transcriptomic profiling of two layer strains throughout the entire production period
Omotoso, A. O., Reyer, H., Oster, M., Ponsuksili, S., Trakooljul, N., Muráni, E., Sommerfeld, V., Rodehutscord, M., & Wimmers, K. (2021) · Scientific Reports · doi:10.1038/s41598-021-99566-5 · Cited by 21
On the horizon: Hedgehog signaling to heal broken bones
Kuwahara, S. T., Liu, S., Chareunsouk, A., Serowoky, M. A., & Mariani, F. V. (2022) · Bone Research · doi:10.1038/s41413-021-00184-8 · Cited by 23
CD317-Positive Immune Stromal Cells in Human “Mesenchymal Stem Cell” Populations
Kay, A. G., Fox, J. M., Hewitson, J. P., Stone, A. P., Robertson, S., James, S. R., Wang, X., Kapasa, E., Yang, X., & Genever, P. G. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.903796 · Cited by 21
Metabolic crosstalk between stromal and malignant cells in the bone marrow niche
Tirado, H. A., Balasundaram, N., Laaouimir, L., Erdem, A., & van Gastel, N. (2023) · Bone Reports · doi:10.1016/j.bonr.2023.101669 · Cited by 25
Labella, R., Vujačić, M., & Trivanović, D. I. (2023) · Stem Cell Reviews and Reports · doi:10.1007/s12015-023-10531-3 · Cited by 21
“Progenitors of Bone Marrow Adipocytes The majority of the literature claims that BMAT develops from BMSCs, where BMAd precursors share the features of osteoblasts, expressing Leptin receptor [13], Osterix [14], and Nestin [15] [Table 2], as described in animal models.”
BackgroundCao, J., Jin, L., Yan, Z., Wang, X., Li, Y., Wang, Z., Liu, Y.-W., Li, H.-M., Guan, Z., He, Z., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-44312-w · Cited by 20
“Despite the above identi fi cation of ECs expressing Prrx1 and Lepr , previous studies have reported that a Lepr-Cre mouse model does not labelECsinbonesections and a Prrx1-Cre mouse modelmarksminimal CD31 + cellsin fl owcytometry 13,20 .”
Pericytes as the Orchestrators of Vasculature and Adipogenesis
Picoli, C. C., Birbrair, A., & Li, Z. (2024) · Genes · doi:10.3390/genes15010126 · Cited by 21
“LepR + cells have the potential to differentiate into osteoblasts, chondrocytes, and adipocytes [73].”
BackgroundInfluentialPeriyasamy‐Thandavan, S., Herberg, S., Arounleut, P., Upadhyay, S. K., Dukes, A., Davis, C., Johnson, M. H., McGee‐Lawrence, M. E., Hamrick, M. W., Isales, C. M., et al. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.03.001 · Cited by 21
“It has been shown that BMSCs have leptin receptors and leptin signaling is required for downstream CXCR4 effects (Zhou et al., 2014).”
The human and murine hematopoietic stem cell niches: are they comparable?
van Pel, M., Fibbe, W. E., & Schepers, K. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12994 · Cited by 21
He, Q., Swindle, C. S., Wan, C., Flynn, R. J., Oster, R. A., Chen, D., Zhang, F., Shu, Y., & Klug, C. A. (2016) · Stem Cells · doi:10.1002/stem.2481 · Cited by 21
Hematopoietic Stem Cells in Neural-crest Derived Bone Marrow
Jiang, N., Chen, M., Yang, G., Xiang, L., He, L., Hei, T. K., Chotkowski, G., Tarnow, D. P., Finkel, M., Ding, L., et al. (2016) · Scientific Reports · doi:10.1038/srep36411 · Cited by 21
The Generic Facet of Hox Protein Function
Saurin, A. J., Delfini, M.-C., Maurel-Zaffran, C., & Graba, Y. (2018) · Trends in Genetics · doi:10.1016/j.tig.2018.08.006 · Cited by 21
Effects of Obesity and Exercise on Bone Marrow Progenitor Cells after Radiation
Emmons, R. S., Ngu, M., Xu, G. B., Hernández‐Saavedra, D., Chen, H., & Lisio, M. D. (2019) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000001894 · Cited by 21
Čamernik, K., Mihelič, A., Mihalič, R., Marolt, D., Janež, A., Trebše, R., Marc, J., & Zupan, J. (2020) · Stem Cell Reviews and Reports · doi:10.1007/s12015-020-09964-x · Cited by 21
“tin receptor [9], ITGAV [6], platelet-derived growth factor receptor (PDGFR)α, PDGFRβ, chondroitin sulfate proteoglycan 4 (CSPG4/NG2) [29, 30], and nerve growth factor receptor (NGFR/CD271) [1], and some populations identified in nonskeletal tissues, such as PEG3 (paternally expressed 3, PW1) [31], neural cell adhesio…”
BackgroundInfluentialMembrane-bound SCF and VCAM-1 synergistically regulate the morphology of hematopoietic stem cells
Hao, J., Zhou, H., Nemes, K., Yen, D. P., Zhao, W., Bramlett, C. S., Wang, B., Lu, R., & Shen, K. (2021) · The Journal of Cell Biology · doi:10.1083/jcb.202010118 · Cited by 21
Adult Prg4+ progenitors repair long-term articular cartilage wounds in vivo
Massengale, M., Massengale, J. L., Benson, C. R., Barywano, N., Oki, T., Steinhauser, M. L., Wang, A., Balani, D., Oh, L. S., Randolph, M. A., et al. (2023) · JCI Insight · doi:10.1172/jci.insight.167858 · Cited by 20
“Fate mapping using constitutive Cre constructs (3, 4) showed that”
BackgroundMethodResultInfluentialGao, L., Lee, H. J., Goodman, J. H., & Ding, L. (2024) · Cell · doi:10.1016/j.cell.2024.03.032 · Cited by 20
Prasad, P., & Cancelas, J. A. (2024) · Cells · doi:10.3390/cells13110910 · Cited by 21
“Within the BM, LepR + cells, the endothelial cell and adipocytes produce SCF, where LepR + MSCs represent its main source [3,20,27,43].”
BackgroundInfluentialSystemic and local regulation of hematopoietic homeostasis in health and disease
Carpenter, R. S., & Maryanovich, M. (2024) · Nature Cardiovascular Research · doi:10.1038/s44161-024-00482-4 · Cited by 24
Fibrinolytic crosstalk with endothelial cells expands murine mesenchymal stromal cells
Dhahri, D., Sato-Kusubata, K., Ohki, M., Nishida, C., Tashiro, Y., Munakata, S., Shimazu, H., Salama, Y., Eiamboonsert, S., Nakauchi, H., et al. (2016) · Blood · doi:10.1182/blood-2015-10-673103 · Cited by 20
Hematopoietic stem cell metabolism and stemness
Huang, D., Chen, C., Xie, L., Yu, Z., & Zheng, J. (2019) · Blood Science · doi:10.1097/bs9.0000000000000012 · Cited by 21
Inhibition of TGFβ improves hematopoietic stem cell niche and ameliorates cancer-related anemia
Wang, B., Wang, Y., Chen, H., Yao, S., Lai, X., Qiu, Y., Cai, J., Huang, Y., Wei, X., Guan, Y., et al. (2021) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-02120-9 · Cited by 20
“As for the condition of MSC, we applied Nestin-GFP transgene mice to sort the Nestin-GFP bone marrow MSC [36, 37] and analyzed the mRNA expression of TGFβ target genes.”
MethodLyu, P., Li, B., Li, P., Bi, R., Cui, C., Zhao, Z., Zhou, X., & Fan, Y. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.654715 · Cited by 21
“Zhou et al. (2014) recently discovered that a small proportion of bone marrow cells express LepR, a marker highly enriched in BMMSCs.”
BackgroundXian, J., Liang, D., Zhao, C., Chen, Y., & Zhu, Q. A. (2022) · Experimental Cell Research · doi:10.1016/j.yexcr.2022.113034 · Cited by 20
Drug Protein‐Stabilized Biomimetic Amorphous Mineral Nanoparticles as Superior Drug Carriers
Lei, J., Zheng, Y., Meng, Y., Wang, F., Feng, Y., Wang, H., Mao, L., Yu, S., & Wang, Z. (2022) · Advanced Functional Materials · doi:10.1002/adfm.202202928 · Cited by 20
A murine model of large-scale bone regeneration reveals a selective requirement for Sonic Hedgehog
Serowoky, M. A., Kuwahara, S. T., Liu, S., Vakhshori, V., Lieberman, J. R., & Mariani, F. V. (2022) · npj Regenerative Medicine · doi:10.1038/s41536-022-00225-8 · Cited by 20
The mechanism of bone repair: Stem cells in the periosteum dedicated to bridging a large gap
Ono, N. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100807 · Cited by 20
“BMSCs marked by Lepr-cre represents a major source of osteoblasts in adult bone marrow.(6) LepR cells also express CXCL12 (LepRCXCL12 cells) and are composed of pre-osteoblast-like and pre-adipocyte-like cells.”
BackgroundWang, J., & Shang, P. (2022) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2022.12.007 · Cited by 20
Austin, M. J., Kalampalika, F., Cawthorn, W. P., & Patel, B. G. (2023) · British Journal of Haematology · doi:10.1111/bjh.18748 · Cited by 23
Organoid Culture Development for Skeletal Systems
Qing, J., Guo, Q., Lv, L., Zhang, X., Liu, Y., Heng, B. C., Li, Z., Zhang, P., & Zhou, Y. (2023) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2023.0022 · Cited by 21
“64 These cell types include P a S cells (cells express PDGFR a and Sca-1), 61 Nestin-expressing cells, 62 and cells expressing leptin receptor (LepR).”
Towards single cell encapsulation for precision biology and medicine
Gupta, P., Alheib, O., & Shin, J. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.115010 · Cited by 22
Mesenchymal Progenitor Cells for the Osteogenic Lineage
Ono, N., & Kronenberg, H. M. (2015) · Current Molecular Biology Reports · doi:10.1007/s40610-015-0017-z · Cited by 20
Hempel, U., Müller, K., Preißler, C., Noack, C., Boxberger, S., Dieter, P., Bornhäuser, M., & Wobus, M. (2016) · Stem Cells International · doi:10.1155/2016/7842191 · Cited by 20
“…supplemented recently by leptin receptor as a marker of 2 Stem Cells International osteogen/adipogen predetermined cells in the bone marrow niche [13]. hBMSC populations isolated from bone marrow aspirates revealed a broad heterogeneity predetermined by actual bone marrow niche composition, by…”
Chin, C. J., Li, S., Corselli, M., Casero, D., Zhu, Y., He, C. B., Hardy, R., Péault, B., & Crooks, G. M. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.12.005 · Cited by 20
“hPSC-derived CD146CD73 mesenchyme showed high expression of NES, LEPR, and CSPG4, markers of peri-sinusoidal and peri-arteriolar cells in the murine HSC niche (Ding et al., 2012; Kunisaki et al., 2013; Méndez-Ferrer et al., 2010; Zhou et al., 2014).”
BackgroundPromyelocytic leukemia protein in mesenchymal stem cells is essential for leukemia progression
de Alvarenga, É. C., da Silva, W. N., Vasconcellos, R., Paredes‐Gamero, E. J., Mintz, A., & Birbrair, A. (2018) · Annals of Hematology · doi:10.1007/s00277-018-3463-x · Cited by 20
Qin, Y., Tang, S., Zhen, G., Ding, Q., Ding, S., & Cao, X. (2018) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13941 · Cited by 20
Li, X., Yang, S., Qin, L., & Yang, S. (2021) · Stem Cells Translational Medicine · doi:10.1002/sctm.20-0424 · Cited by 20
Kimura, K., Breitbach, M., Schildberg, F. A., Hesse, M., & Fleischmann, B. K. (2021) · Bone Reports · doi:10.1016/j.bonr.2021.101133 · Cited by 20
“Elegant fate mapping studies have revealed that Lepr-cre and Cxcl12creER BM stromal cells respond to stress and contribute to bone regeneration during fracture healing (Zhou et al., 2014) (Matsushita et al.”
BackgroundWang, T., Yang, L., Liang, Z., Bai, L., Pei, H., Zhang, T., Wu, L., Wang, L., Wang, X., You, X., et al. (2021) · Biomaterials Advances · doi:10.1016/j.msec.2021.112635 · Cited by 20
Zhang, P., Xing, C., Rhodes, S. D., He, Y., Deng, K., Li, Z., He, F., Zhu, C., Nguyen, L., Zhou, Y., et al. (2016) · Stem Cell Reports · doi:10.1016/j.stemcr.2016.04.013 · Cited by 22
“To determine whether the BMSC frequency is affected in OsxCre;Asxl1D/D mice, we examined the percentage of PDGFRa+CD45 TER119 CD31 BMSCs by flow cytometry (Worthley et al., 2015; Zhou et al., 2014).”
BackgroundThe bone marrow hematopoietic niche and its adaptation to infection
Gomes, A. C., Saraiva, M., & Gomes, M. S. (2021) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2020.05.014 · Cited by 18
Tenascin-C promotes bone regeneration via inflammatory macrophages
Ren, Q., Xing, W., Jiang, B., Feng, H., Hu, X., Suo, J., Wang, L., & Zou, W. (2025) · Cell Death and Differentiation · doi:10.1038/s41418-024-01429-9 · Cited by 24
“RNA-seq data has been uploaded in fi gshare.com, https:// doi.org/10.6084/m9. fi gshare.27328593.v1.”
InfluentialWang, W., Strecker, S. E., Liu, Y., Wang, L., Assanah, F., Smith, S. S., & Maye, P. F. (2014) · Bone · doi:10.1016/j.bone.2014.10.005 · Cited by 19
“While the perivascular stromal localization of CTGF+ cells was consistent with an increasing body of work suggesting that perivascular stromal/reticular cells may be the source of BMSCs [11,15,16], the localization of CTGF+ cells was not limited to vascular structures, being also found adjacent to osteoblasts and in t…”
InfluentialMesenchymal lineage cells and their importance in B lymphocyte niches
Green, A., Rudolph-Stringer, V., Chantry, A., Wu, J. Y., & Purton, L. (2017) · Bone · doi:10.1016/j.bone.2017.11.018 · Cited by 18
Dadras, M., May, C., Wagner, J. M., Wallner, C., Becerikli, M., Dittfeld, S., Serschnitzki, B., Schilde, L. M., Guntermann, A., Sengstock, C., et al. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15797 · Cited by 19
The Cellular Choreography of Osteoblast Angiotropism in Bone Development and Homeostasis
Neag, G., Finlay, M., & Naylor, A. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147253 · Cited by 19
“Recent studies provide evidence that geographical location within the bone can modulate lineage commitment potential, most likely due to the direct influence of signalling of cells in the near vicinity [22,74,76].”
BackgroundToward Marrow Adipocytes: Adipogenic Trajectory of the Bone Marrow Stromal Cell Lineage
Matsushita, Y., Ono, W., & Ono, N. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.882297 · Cited by 19
“LepR+ stromal cells provide a major source of adipocytes in adult bone marrow (38), which is further supported by more recent lineage-tracing studies using Lepr-creER (39).”
BackgroundResultInfluentialSLC38A2 provides proline and alanine to regulate postnatal bone mass accrual in mice
Shen, L., Yu, Y., & Karner, C. M. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.992679 · Cited by 20
“Osteoblasts differentiate from multipotent skeletal stem and progenitor cells (SSPC) that reside in the bone marrow and periosteum (Mizoguchi et al., 2014; Zhou et al., 2014; Bianco and Robey, 2015; Debnath et al., 2018).”
BackgroundInfluentialDifferential regulation of skeletal stem/progenitor cells in distinct skeletal compartments
Solidum, J. G. N., Jeong, Y., Heralde, F. M., & Park, D. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1137063 · Cited by 20
“LepR cells are observed only in postnatal perisinusoidal or periarteriolar BM-SSPCs (Zhou et al., 2014; Shen et al., 2021) that are largely overlapping with the Cxcl12abundant reticular (CAR) cells (Matsushita et al.”
BackgroundWHIM Syndrome-linked CXCR4 mutations drive osteoporosis
Anginot, A., Nguyen, J., Nader, Z. A., Rondeau, V., Bonaud, A., Kalogeraki, M., Boutin, A., Lemos, J. P., Bisio, V., Koenen, J., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37791-4 · Cited by 20
Nowak, W. N., Taha, H., Kachamakova‐Trojanowska, N., Stępniewski, J., Markiewicz, J., Kusienicka, A., Szade, K., Szade, A., Bukowska-Straková, K., Hajduk, K., et al. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7097 · Cited by 20
“(36), leptin receptor LepR (8, 67), or high expression of CXCL12 (41).”
Enhanced engraftment of human myelofibrosis stem and progenitor cells in MISTRG mice
Lysenko, V., van Wijk, N. W.-V., Zimmermann, K., Weller, M.-C., Bühler, M. M., Wildschut, M. H. E., Schürch, P. M., Fritz, C., Wagner, U., Calabresi, L., et al. (2020) · Blood Advances · doi:10.1182/bloodadvances.2019001364 · Cited by 19
“Leptin-receptor–positive and Gli1(1) mesenchymal stromal cells transform into fibrosis-driving cells through stimulation by platelet-derived growth factor a (PDGFa) and CXC chemokine ligand 4 (CXCL4), secreted by megakaryocytes.(34,36,37) The sequence homology between mouse and human for TGFb1 (89.”
BackgroundANGPTL4 binds to the leptin receptor to regulate ectopic bone formation
Hu, H., Luo, S., Lai, P., Lai, M., Mao, L., Zhang, S., Jiang, Y., Wen, J., Zhou, W., Liu, X., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2310685120 · Cited by 18
Singh, A. K., Prasad, P., & Cancelas, J. A. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1325291 · Cited by 21
Xie, J., Lou, Q., Zeng, Y., Liang, Y., Xie, S., Xu, Q., Yuan, L., Wang, J., Jiang, L., Mou, L., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.653308 · Cited by 18
“This is consistent with previous reports that multipotent MSCs are quiescent (Mendez-Ferrer et al., 2010; Zhou et al., 2014).”
BackgroundMethodResultInfluentialGli1+ Osteogenic Progenitors Contribute to Condylar Development and Fracture Repair
Chen, S., Lin, L., Lei, J., He, Y., & Zhang, Y. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.819689 · Cited by 18
Disruption of stem cell niche–confined R-spondin 3 expression leads to impaired hematopoiesis
Kurtova, A. V., Heinlein, M., Haas, S. F., Velten, L., Dijkgraaf, G. J. P., Storm, E. E., Kljavin, N. M., Boumahdi, S., Himmels, P., Hérault, A., et al. (2022) · Blood Advances · doi:10.1182/bloodadvances.2022007714 · Cited by 18
“1,39 These stromal cells are also the predominant source of RSPO3 in a publicly available bone marrow scRNA-seq data set 40 that includes LepR + stromal cells, collagen Col2.”
BackgroundAge-associated declining of the regeneration potential of skeletal stem/progenitor cells
Mancinelli, L., & Intini, G. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1087254 · Cited by 20
Complexities of modeling the bone marrow microenvironment to facilitate hematopoietic research
Busch, C., Nyamondo, K., & Wheadon, H. (2024) · Experimental Hematology · doi:10.1016/j.exphem.2024.104233 · Cited by 18
A latent Axin2+/Scx+ progenitor pool is the central organizer of tendon healing
Grinstein, M., Tsai, S. L., Montoro, D. T., Freedman, B. R., Dingwall, H. L., Villaseñor, S., Zou, K., Sade-Feldman, M., Tanaka, M. J., Mooney, D. J., et al. (2024) · npj Regenerative Medicine · doi:10.1038/s41536-024-00370-2 · Cited by 21
de Kruijf, E.-J. F. M., Zuijderduijn, R., Stip, M. C., Fibbe, W. E., & van Pel, M. (2018) · Experimental Hematology · doi:10.1016/j.exphem.2018.05.002 · Cited by 18
Synovium-Derived Mesenchymal Stem/Stromal Cells and their Promise for Cartilage Regeneration
Zupan, J., Drobnič, M., & Stražar, K. (2019) · Advances in experimental medicine and biology · doi:10.1007/5584_2019_381 · Cited by 18
Zeng, Y. C., Li, B., Li, T., Liu, W., Ran, C., Penson, R. T., Poznansky, M. C., Du, Y., & Chen, H. (2019) · Oncotarget · doi:10.18632/oncotarget.27065 · Cited by 18
“It should also be good to screen and purify CD90low MSC population, and further detect markers indicated in other research for subpopulation identification, such as CD146 (a marker related to supporting hematopoiesis) [58, 59], LepR (a marker related to enhanced osteogenic differentiation) [60] and CXCR4 (a marker rel…”
BackgroundAdipogenesis in Different Body Depots and Tumor Development
Trivanović, D. I., Vignjević, S., Djordjević, I. O., Кукољ, Т., Bugarski, D. S., & Jauković, A. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.571648 · Cited by 18
Soto, C. A., Celso, C. L., Purton, L. E., & Frisch, B. J. (2021) · JBMR Plus · doi:10.1002/jbm4.10516 · Cited by 19
Kaastrup, K., & Grønbæk, K. (2021) · HemaSphere · doi:10.1097/hs9.0000000000000615 · Cited by 18
Vascular Regulation of Hematopoietic Stem Cell Homeostasis, Regeneration, and Aging
Ramalingam, P., Butler, J. M., & Poulos, M. G. (2021) · Current Stem Cell Reports · doi:10.1007/s40778-021-00198-2 · Cited by 18
Stem cells and bone diseases: New tools, new perspective
Riminucci, M., Remoli, C., Robey, P. G., & Bianco, P. (2014) · Bone · doi:10.1016/j.bone.2014.09.009 · Cited by 18
“However, recent data in the mouse directly support the general key concept that perivascular stromal skeletal stem cells (otherwise known as bone marrow-derived “mesenchymal” stem cells [16]) act both as progenitors for skeletal tissues and as key players of the perivascular HME/niche also in themouse [11,13].”
Extrinsic regulation of hematopoietic stem cells in development, homeostasis and diseases
Lee, Y., Decker, M., Lee, H. J., & Ding, L. (2017) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.279 · Cited by 20
“As described above, MSCs are a key component of the HSC niche and can differentiate into adipocytes, osteoblasts and chondrocytes within the bone marrow.(86,166) Old bone marrow MSCs are less proliferative, less likely to differentiate into osteoblasts, more likely to differentiate into adipocytes, and more apoptotic…”
BackgroundOverview of Skeletal Development
Kobayashi, T., & Kronenberg, H. M. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-1028-2_1 · Cited by 17
Buchan, H., Gray, M., Hill, A., & Coulter, A. (1990) · PubMed · Cited by 18
Qu, Y., Sun, Z., Yuan, Y., Li, Z., Wang, F., Wu, K., Yu, H., Lin, Q., He, F., Chen, J., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05080-5 · Cited by 17
“As shown in present and other studies [35, 36], intra-BM adipocytes are Y.”
ResultThe emerging studies on mesenchymal progenitors in the long bone
Shen, F., Huang, X., He, G., & Shi, Y. (2023) · Cell & Bioscience · doi:10.1186/s13578-023-01039-x · Cited by 19
Janeczek, A. A., Tare, R. S., Scarpa, E., Moreno-Jiménez, I., Rowland, C. A., Jenner, D. C., Newman, T. A., Oreffo, R. O. C., & Evans, N. D. (2015) · Stem Cells · doi:10.1002/stem.2241 · Cited by 16
Tsunokuma, N., Yamane, T., Matsumoto, C., Tsuneto, M., Isono, K., Imanaka‐Yoshida, K., & Yamazaki, H. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1502592 · Cited by 17
“LepR-expressing cells that were localized to the perivascular areas comprise ∼0.3% of BM cells and represent the main source of boneforming cells in the adult BM; these LepR+ cells strongly express Scf and Cxcl12 (61).”
BackgroundInfluentialThe known molecules involved in MSC homing and migration
Nazari, H. G. (2018) · Journal of Stem Cell Research and Medicine · doi:10.15761/jscrm.1000127 · Cited by 17
The haematopoietic stem cell niche: a new player in cardiovascular disease?
Al‐Sharea, A., Lee, M. K. S., Purton, L. E., Hawkins, E. D., & Murphy, A. J. (2018) · Cardiovascular Research · doi:10.1093/cvr/cvy308 · Cited by 18
Zuckerman, P. C., Liu, C., Cai, C., Mahaffey, I., Norman, S. C., Cole, W., & Castillo, A. B. (2019) · JBMR Plus · doi:10.1002/jbm4.10199 · Cited by 17
“Bone marrow contains multipotent mesenchymal stromal cells that have been identified by various overlapping markers including LepR,(25) CXCL12,(26) Sca‐1,(24,27) CD166,(24) PDGFRa,(27) Nestin,(28) NG2,(29) and Gremlin 1.”
BackgroundInfluentialBone regeneration via skeletal cell lineage plasticity: All hands mobilized for emergencies
Matsushita, Y., Ono, W., & Ono, N. (2020) · BioEssays · doi:10.1002/bies.202000202 · Cited by 19
“Some studies examining the function of potential skeletal stem cell populations rely on a “constitutively active” version of cre recombinases, such as Prrx1cre[35] andCtsk-cre[16] for the periosteum, and LepR-cre[46] for the bone marrow.”
BackgroundResultLow‐Dose Tamoxifen Induces Significant Bone Formation in Mice
Xie, Z., McGrath, C., Sankaran, J. S., Styner, M., Little, S. E., Dudakovic, A., van Wijnen, A. J., Rubin, J. E., & Sen, B. (2020) · JBMR Plus · doi:10.1002/jbm4.10450 · Cited by 17
Bone Marrow Stromal Cell Assays: In Vitro and In Vivo
Robey, P. G., Kuznetsov, S. A., Bianco, P., & Riminucci, M. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-1028-2_23 · Cited by 17
Provot, S., Schipani, E., Wu, J. Y., & Kronenberg, H. M. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-415853-5.00006-6 · Cited by 18
Borriello, A., Caldarelli, I., Bencivenga, D., Stampone, E., Perrotta, S., Oliva, A., & Ragione, F. D. (2016) · Oncotarget · doi:10.18632/oncotarget.12649 · Cited by 16
“In addition to the markers listed above, others need to be considered with peculiar attention, namely: nestin (Nes), receptor of leptin (LepR), stem cell factor (SCF), C-X-C motif chemokine ligand 12 (CXCL12), neural/ glial antigen 2 (NG2), paired related homeobox 1 protein (Prx1), myxovirus resistance-1 (Mx1), platel…”
BackgroundInfluentialSicco, C. L., Reverberi, D., Villa, F., Pfeffer, U., Quarto, R., Cancedda, R., & Tasso, R. (2018) · Stem Cell Research & Therapy · doi:10.1186/s13287-018-1056-1 · Cited by 17
“Narcisi R, Cleary MA, Brama PAJ, Hoogduijn MJ, Tüysüz N, ten Berge D, et al. Long-term expansion, enhanced chondrogenic potential, and suppression of endochondral ossification of adult human MSCs via WNT signaling modulation.”
BackgroundInfluentialObesity and leptin influence vitamin D metabolism and action in human marrow stromal cells
Li, J., Gao, Y., Yu, T., Lange, J. K., LeBoff, M. S., Górska, A., Luu, S., Zhou, S., & Glowacki, J. (2019) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2019.105564 · Cited by 17
Regulation of Hematopoietic Stem Cell Fate and Malignancy
Cho, H. J., Lee, J., Yoon, S. R., Lee, H. G., & Jung, H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21134780 · Cited by 18
“Perivascular stromal cells play a critical role in the regulation of HSCs and localize near both HSCs and endothelial cells [51].”
BackgroundMeeting report of the 2016 bone marrow adiposity meeting
van der Eerden, B. V. D., & VanWijnen, A. (2017) · Adipocyte · doi:10.1080/21623945.2017.1313374 · Cited by 9
“set of experiments, the majority of CFU-Fs (94%) were found to be traced by expression of the leptin receptor (Lepr) (45).”
BackgroundUnveiling novel insights in acute myeloid leukemia through single-cell RNA sequencing
Zhou, J., & Chng, W. J. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1365330 · Cited by 22
“LepR + cells are key components of the BM hematopoietic microenvironment, and involved in regulating hematopoiesis, bone formation and remodeling (83, 84).”
BackgroundLim, J. J., Vining, K. H., Mooney, D. J., & Blencowe, B. J. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2404146121 · Cited by 16
“We then independently clustered stromal cells that were identified by the expression of MSC markers, LEPR and CXCL12 (72) ( SI Appendix , Fig.”
Function of hematopoiesis and bone marrow niche in inflammation and non-hematopoietic diseases
Wang, Y., Deng, Z., Li, Y.-Y., Bai, K., Ma, J., Liu, Y., & Chen, Q. (2025) · Life Medicine · doi:10.1093/lifemedi/lnaf015 · Cited by 19
“The importance of CAR cells is evidenced by their ablation, which leads to a reduction in the HSCs population due to robust decrease of CXCL12 and SCF production [25].”
Mohrin, M., Liu, J., Zavala‐Solorio, J., Bhargava, S., Trumble, J. M., Brito, A., Hu, D. Z., Brooks, D. J., Κούκος, Γ., Alabdulaaly, L., et al. (2021) · Aging Cell · doi:10.1111/acel.13313 · Cited by 20
Odontoblast death drives cell-rich zone-derived dental tissue regeneration
Zhao, L., Ito, S., Arai, A., Udagawa, N., Horibe, K., Hara, M., Nishida, D., Hosoya, A., Masuko, R., Okabe, K., et al. (2021) · Bone · doi:10.1016/j.bone.2021.116010 · Cited by 16
Hematopoietic stem cell regeneration through paracrine regulation of the Wnt5a/Prox1 signaling axis
Lin, Q., Wu, L., Chatla, S., Chowdhury, F. A., Atale, N., Joseph, J., & Du, W. (2022) · Journal of Clinical Investigation · doi:10.1172/jci155914 · Cited by 16
“The BM also contains a variety of nonhematopoietic components, including endosteal and sinusoidal endothelial cells, mesenchymal stromal cells (MSCs), and osteoblast-lineage cells (1, 2, 4, 5).”
InfluentialJia, Y., Wang, A., Zhao, B., Wang, C., Su, R., Zhang, B., Fan, Z., Zeng, Q., He, L., Pei, X., et al. (2022) · Cell Proliferation · doi:10.1111/cpr.13300 · Cited by 15
Leptin receptor in osteocytes promotes cortical bone consolidation in female mice
Wee, N. K. Y., de Lima, T. F. C., McGregor, N. E., Walker, E. C., Poulton, I. J., Blank, M., & Sims, N. A. (2022) · Journal of Endocrinology · doi:10.1530/joe-22-0084 · Cited by 15
Oka, H., Ito, S., Kawakami, M., Sasaki, H., Abe, S., Matsunaga, S., Morita, S., Noguchi, T., Kasahara, N., Tokuyama, A., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-30446-w · Cited by 16
Chen, H., Xiao, H., Wu, B., Shi, X., Guan, C., Hu, J., Zhang, T., & Lü, H. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.09.012 · Cited by 16
“For example, CD146 + MSC [29] and LepR + MSC [30] have stronger osteogenic differentiation potential, and CD271 + MSC exhibit stronger chondrogenic ability than common MSCs [31].”
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
