{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:58:53Z","timestamp":1790812733684,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T00:00:00Z","timestamp":1664150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31960136"],"award-info":[{"award-number":["31960136"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81960268"],"award-info":[{"award-number":["81960268"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Sarcopenia is defined as an age\u2010related progressive loss of muscle mass and\/or strength. Although different factors can contribute to this disease, the underlying mechanisms remain unclear. We assessed transcriptional heterogeneity in skeletal muscles from sarcopenic and control mice at single\u2010cell resolution.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A mouse model was established to study sarcopenic skeletal muscles. Single\u2010cell RNA\u2010seq was performed on tibialis anterior (TA) muscle cells collected from sarcopenic and control mice. A series of bioinformatic analyses were carried out to identify and compare different cell types under different conditions. Immunofluorescence staining and western blotting were used to validate the findings from single\u2010cell experiments. Tube formation assays were conducted to further evaluate the effects of Gbp2 on endothelial cells during angiogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A murine sarcopenia model was successfully established using a senescence\u2010accelerated mouse strain (SAMP6, <jats:italic>n<\/jats:italic>\u00a0=\u00a05). Sarcopenia phenotype was induced by administration of dexamethasone (20\u00a0mg\/kg) and reduced physical activity. Senescence\u2010resistant mice strain (SAMR1) and SAMP6 strain with similar activity but injected with PBS were recruited as two control groups. As signs of sarcopenia, body weight, muscle cell counts and cross\u2010sectional fibre area were all significantly decreased in sarcopenic mice (<jats:italic>P value\u00a0=\u00a00.004<\/jats:italic>, <jats:italic>0.03 and 0.035<\/jats:italic>, respectively). After quality control, 13\u2009612 TA muscle single\u2010cell transcriptomes were retained for analysis. Fourteen cell clusters were identified from the profiled cells. Among them, two distinct endothelial subtypes were found to be dominant in the sarcopenia group (42.2% cells) and in the two control groups (59.1% and 47.9% cells), respectively. 191 differentially expressed genes were detected between the two endothelial subtypes. Sarcopenia\u2010specific endothelial cell subtype exhibited a dramatic increase in the interferon family genes and the interferon\u2010inducible guanylate\u2010binding protein (GBP) family gene expressions. For example, <jats:italic>Igtp<\/jats:italic> and <jats:italic>Gbp2<\/jats:italic> in sarcopenic endothelial cells were 5.4 and 13.3 times higher than those in the control groups, respectively. We further validated our findings in muscle specimens of sarcopenia patients and observed that GBP2 levels were increased in endothelial cells of a subset of patients (11 of 40 patients, 27.5%), and we identified significantly higher CD31 and GBP2 co\u2010localization (<jats:italic>P value\u00a0=\u00a00.001128<\/jats:italic>). Finally, we overexpressed <jats:italic>Gbp2<\/jats:italic> in human umbilical vein endothelial cells <jats:italic>in vitro<\/jats:italic>. The endothelial cells with elevated <jats:italic>Gbp2<\/jats:italic> expression displayed compromised tube formation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our single\u2010cell\u2010based results suggested that endothelial cells may play critical roles in sarcopenia development through interferon\u2010GBP signalling pathways, highlighting new therapeutic directions to slow down or even reverse age\u2010related sarcopenia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13091","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T19:40:18Z","timestamp":1664221218000},"page":"2985-2998","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Single\u2010cell RNA\u2010seq reveals interferon\u2010induced guanylate\u2010binding proteins are linked with sarcopenia"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7567-0143","authenticated-orcid":false,"given":"Zhi","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery the First People's Hospital of Yunnan Province, the Affiliated Hospital of Kunming University of Science and Technology, the Key Laboratory of Digital Orthopaedics of Yunnan Provincial  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5672-5527","authenticated-orcid":false,"given":"Ruoyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"InnoVec Biotherapeutics Co., Ltd  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Kuang","sequence":"additional","affiliation":[{"name":"the First Department of Hepatic Diseases the Third People's Hospital of Kunming City  Kunming Yunnan 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7532-8981","authenticated-orcid":false,"given":"Sheng","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery the First People's Hospital of Yunnan Province, the Affiliated Hospital of Kunming University of Science and Technology, the Key Laboratory of Digital Orthopaedics of Yunnan Provincial  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,26]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"177","article-title":"Clinical definition of sarcopenia","volume":"11","author":"Santilli V","year":"2014","journal-title":"Clin Cases Miner Bone 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