{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:54:31Z","timestamp":1791654871529,"version":"4.3.4"},"reference-count":56,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,7,8]],"date-time":"2020-07-08T00:00:00Z","timestamp":1594166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001642","name":"Glenn Foundation for Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001642","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":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Persistent loss of skeletal muscle mass and function as well as altered fat metabolism are frequently observed in severe sepsis survivors. Studies examining sepsis\u2010associated tissue dysfunction from the perspective of the tissue microenvironment are scarce. In this study, we comprehensively assessed transcriptional changes in muscle and fat at single\u2010cell resolution following experimental sepsis induction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Skeletal muscle and visceral white adipose tissue from control mice or mice 1\u00a0day or 1\u00a0month following faecal slurry\u2010induced sepsis were used. Single cells were mechanically and enzymatically prepared from whole tissue, and viable cells were further isolated by fluorescence activated cell sorting. Droplet\u2010based single\u2010cell RNA\u2010sequencing (scRNA\u2010seq; 10\u00d7 Genomics) was used to generate single\u2010cell gene expression profiles of thousands of muscle and fat\u2010resident cells. Bioinformatics analyses were performed to identify and compare individual cell populations in both tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In skeletal muscle, scRNA\u2010seq analysis classified 1438 single cells into myocytes, endothelial cells, fibroblasts, mesenchymal stem cells, macrophages, neutrophils, T\u2010cells, B\u2010cells, and dendritic cells. In adipose tissue, scRNA\u2010seq analysis classified 2281 single cells into adipose stem cells, preadipocytes, endothelial cells, fibroblasts, macrophages, dendritic cells, B\u2010cells, T\u2010cells, NK cells, and gamma delta T\u2010cells. One day post\u2010sepsis, the proportion of most non\u2010immune cell populations was decreased, while immune cell populations, particularly neutrophils and macrophages, were highly enriched. Proportional changes of endothelial cells, neutrophils, and macrophages were validated using faecal slurry and cecal ligation and puncture models. At 1\u00a0month post\u2010sepsis, we observed persistent enrichment\/depletion of cell populations and further uncovered a cell\u2010type and tissue\u2010specific ability to return to a baseline transcriptomic state. Differential gene expression analyses revealed key genes and pathways altered in post\u2010sepsis muscle and fat and highlighted the engagement of infection\/inflammation and tissue damage signalling. Finally, regulator analysis identified gonadotropin\u2010releasing hormone and Bay 11\u20107082 as targets\/compounds that we show can reduce sepsis\u2010associated loss of lean or fat mass.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data demonstrate persistent post\u2010sepsis muscle and adipose tissue disruption at the single\u2010cell level and highlight opportunities to combat long\u2010term post\u2010sepsis tissue wasting using bioinformatics\u2010guided therapeutic interventions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12596","type":"journal-article","created":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T05:35:08Z","timestamp":1594272908000},"page":"1351-1363","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Single\u2010cell deconstruction of post\u2010sepsis skeletal muscle and adipose tissue 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