{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:40:45Z","timestamp":1784248845142,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA0805903"],"award-info":[{"award-number":["2021YFA0805903"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFD1301200"],"award-info":[{"award-number":["2022YFD1301200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFA0509500"],"award-info":[{"award-number":["2020YFA0509500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32341050"],"award-info":[{"award-number":["32341050"]}],"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":["32272837"],"award-info":[{"award-number":["32272837"]}],"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":["32421005"],"award-info":[{"award-number":["32421005"]}],"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":["32225046"],"award-info":[{"award-number":["32225046"]}],"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":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Heat stress can induce skeletal muscle injury. Typical characteristics of heat\u2010exposed muscle tissues include apoptosis, oxidative stress and autophagy. The understanding of molecular mechanisms underlying heat stress\u2010induced muscle injury is limited, especially at the single\u2010cell transcription level.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We collected skeletal muscles from 12\u2010week\u2010old female C57BL\/6J mice in control (NC) and four heat stress groups. The experimental scheme comprised five groups: NC (25.5\u00b0C\u2009\u00b1\u20090.5\u00b0C), HS0 (after ~3\u2010h heat exposure, 41.5\u00b0C\u2009\u00b1\u20090.5\u00b0C), HS8, HS16 and HS24 group (recovery at 25.5\u00b0C\u2009\u00b1\u20090.5\u00b0C for 8, 16 and 24\u2009h, respectively). Skeletal muscles were subjected to HE staining (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096), TUNEL staining (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093) and transmission electron microscopy (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093). Transcripts were measured at the tissue (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20095 or 6) and single\u2010nucleus levels (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Histologically, myofibrillar structure deformation, mitochondrial swelling and fusion, intramuscular triglyceride accumulation and autophagy occurred in the muscles subjected to heat stress. At the tissue level, a gene cluster associated with the response to heat exhibited an increasing trend of transcription in the HS0 versus NC groups, and the levels decreased to those in the NC group after 16\u2009h. At the single\u2010cell level, 134\u2009320 high\u2010quality myonuclei were collected from the muscles and annotated as seven cell types, including myonuclei, muscle stem cells (MuSCs) and immune cells. We identified the larger number of differentially expressed genes in the myonuclei. After heat stress, new cell clusters appeared in type IIa\/IIx (HS8 group) and IIb (HS0 group) myonuclei but not in type I myonuclei. Generally, immediate early genes, highly expressed genes and transcription factor regulons identified in new cell clusters induced by heat were related to responses to heat, heat shock, oxidative stress and antioxidative stress. To repair the injured muscles, MuSCs highly expressed the development\u2010related genes, such as\n                      <jats:italic>Atp2a1<\/jats:italic>\n                      ,\n                      <jats:italic>Ckm<\/jats:italic>\n                      ,\n                      <jats:italic>Myh1<\/jats:italic>\n                      ,\n                      <jats:italic>Aldoa<\/jats:italic>\n                      ,\n                      <jats:italic>Pde4d<\/jats:italic>\n                      and\n                      <jats:italic>Pdlim5<\/jats:italic>\n                      . Analysis of cell\u2013cell communication showed that\n                      <jats:italic>Dag1<\/jats:italic>\n                      and\n                      <jats:italic>Egf<\/jats:italic>\n                      signals associated with myonuclei were the underlying pathways that participated in repair tissues.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We constructed the largest transcriptomic dataset, to date, for heat\u2010exposed skeletal muscles. At tissue resolution, the response of muscles to heat stress was eliminated after a recovery period of 16\u2009h. At single\u2010nucleus resolution, the myofibre was the most heat\u2010sensitive cell type, and type IIb myonuclei were the most heat\u2010sensitive subtype of myonuclei. To our knowledge, this is the first study to reveal the molecular mechanisms underlying heat\u2010induced muscle injury and repair at the single\u2010cell transcriptional level.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70217","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T09:54:21Z","timestamp":1770890061000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Single\u2010Nucleus Transcriptome Reveals Cellular Heterogeneity and Transcriptional Response to Heat Stress in Skeletal Muscle"],"prefix":"10.1002","volume":"17","author":[{"given":"Ziyin","family":"Han","sequence":"first","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology Sichuan Agricultural University  Chengdu China"},{"name":"Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding Foshan University  Foshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Chongqing Academy of Animal Science  Chongqing China"},{"name":"Key Laboratory of Animal Resource Evaluation and Utilization (Pigs) Ministry of Agriculture and Rural Affairs  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyu","family":"Lei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology Sichuan Agricultural University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaman","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology Sichuan Agricultural University  Chengdu 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