{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T03:56:54Z","timestamp":1791172614933,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T00:00:00Z","timestamp":1606435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004835","name":"Zhejiang University","doi-asserted-by":"publisher","award":["2018YFA0800403"],"award-info":[{"award-number":["2018YFA0800403"]}],"id":[{"id":"10.13039\/501100004835","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31722053"],"award-info":[{"award-number":["31722053"]}],"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":["31672427"],"award-info":[{"award-number":["31672427"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LR17C170001"],"award-info":[{"award-number":["LR17C170001"]}],"id":[{"id":"10.13039\/501100004731","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":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ageing is accompanied by sarcopenia and intramuscular fat (IMAT) infiltration. In skeletal muscle, fat infiltration is a common feature in several myopathies and is associated with muscular dysfunction and insulin resistance. However, the cellular origin and lipidomic and transcriptomic changes during fat infiltration in skeletal muscle remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In the current study, we generated a high IMAT\u2010infiltrated skeletal muscle model by glycerol (GLY) injection. Single\u2010cell RNA sequencing and lineage tracing were performed on GLY\u2010injured skeletal muscle at 5\u00a0days post\u2010injection (DPI) to identify the cell origins and dynamics. Lipidomics and RNA sequencing were performed on IMAT\u2010infiltrated skeletal muscle at 14 DPI (or 17 DPI for the cold treatment) to analyse alterations of lipid compositions and gene expression levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified nine distinct major clusters including myeloid\u2010derived cells (52.13%), fibroblast\/fibro\/adipogenic progenitors (FAPs) (23.24%), and skeletal muscle stem cells (2.02%) in GLY\u2010injured skeletal muscle. Clustering and pseudotemporal trajectories revealed six subpopulations in fibroblast\/FAPs and 10 subclusters in myeloid\u2010derived cells. A subpopulation of myeloid\u2010derived cells expressing adipocyte\u2010enriched genes and Pdgfra\n                      <jats:sup>\u2212<\/jats:sup>\n                      \/Cd68\n                      <jats:sup>+<\/jats:sup>\n                      cells displayed lipid droplets upon adipogenic induction, indicating their adipogenic potential. Lipidomic analysis revealed the changes of overall lipid classes composition (e.g. triglycerides (TAGs) increased by 19.3 times,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0098; sulfoquinovosyl diacylglycerol decreased by 83%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0056) and in the distribution of lipids [e.g. TAGs (18:2\/18:2\/22:6) increased by 181.6 times,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.021] between GLY\u2010group and saline control. RNA\u2010seq revealed 1847 up\u2010regulated genes and 321 down\u2010regulated genes and significant changes in lipid metabolism\u2010related pathways (e.g. glycerolipid pathway and glycerophospholipid pathway) in our model of GLY\u2010injured skeletal muscle. Notably, short\u2010term cold exposure altered fatty acid composition (e.g. saturated fatty acid decreased by 6.4%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.058) in fat\u2010infiltrated muscles through directly affecting lipid metabolism pathways including PI3K\u2013AKT and MAPK signalling pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results showed that a subpopulation of myeloid\u2010derived cells may contribute to IMAT infiltration. GLY\u2010induced IMAT infiltration changed the lipid composition and gene expression profiles. Short\u2010term cold exposure might regulate lipid metabolism and its related signalling pathways in fat\u2010infiltrated muscle. Our study provides a comprehensive resource describing the molecular signature of fat infiltration in skeletal muscle.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.12643","type":"journal-article","created":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T03:44:39Z","timestamp":1606448679000},"page":"109-129","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":125,"title":["Single\u2010cell RNA sequencing and lipidomics reveal cell and lipid dynamics of fat infiltration in skeletal muscle"],"prefix":"10.1002","volume":"12","author":[{"given":"Ziye","family":"Xu","sequence":"first","affiliation":[{"name":"College of Animal Sciences Zhejiang University  Hangzhou Zhejiang China"},{"name":"Key Laboratory of Molecular Animal Nutrition (Zhejiang University) Ministry of Education  Hangzhou China"},{"name":"Laboratory of Animal Feed and Nutrition of Zhejiang Province  Hangzhou 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