{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:21:10Z","timestamp":1792264870449,"version":"4.4.0"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,7,13]],"date-time":"2024-07-13T00:00:00Z","timestamp":1720828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017481","name":"Ulusal Metroloji Enstit\u00fcs\u00fc, T\u00fcrkiye Bilimsel ve Teknolojik Ara\u015ftirma Kurumu","doi-asserted-by":"publisher","award":["122Z163"],"award-info":[{"award-number":["122Z163"]}],"id":[{"id":"10.13039\/501100017481","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":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tumour\u2010induced skeletal muscle wasting in the context of cancer cachexia is a condition with profound implications for patient survival. The loss of muscle mass is a significant clinical obstacle and is linked to reduced tolerance to chemotherapy and increased frailty. Understanding the molecular mechanisms driving muscle atrophy is crucial for the design of new therapeutics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Lewis lung carcinoma tumours were utilized to induce cachexia and muscle atrophy in mice. Single\u2010nucleus libraries of the tibialis anterior (TA) muscle from tumour\u2010bearing mice and their non\u2010tumour\u2010bearing controls were constructed using 10X Genomics applications following the manufacturer's guidelines. RNA sequencing results were analysed with Cell Ranger software and the Seurat R package. Oxygen consumption of mitochondria isolated from TA muscle was measured using an Oroboros O2k\u2010FluoRespirometer. Mouse primary myotubes were treated with a recombinant ectodysplasin A2 (EDA\u2010A2) protein to activate EDA\u2010A2 receptor (EDA2R) signalling and study changes in gene expression and oxygen consumption.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Tumour\u2010bearing mice were sacrificed while exhibiting moderate cachexia. Average TA muscle weight was reduced by 11% (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0207) in these mice. A total of 12\u00a0335 nuclei, comprising 6422 nuclei from the control group and 5892 nuclei from atrophying muscles, were studied. The analysis of single\u2010nucleus transcriptomes identified distinct myonuclear gene signatures and a shift towards type IIb myonuclei. Muscle atrophy\u2010related genes, including\n                      <jats:italic>Atrogin1<\/jats:italic>\n                      ,\n                      <jats:italic>MuRF1<\/jats:italic>\n                      and\n                      <jats:italic>Eda2r<\/jats:italic>\n                      , were upregulated in these myonuclei, emphasizing their crucial roles in muscle wasting. Gene set enrichment analysis demonstrated that EDA2R activation and tumour inoculation led to similar expression patterns in muscle cells, including the stimulation of nuclear factor\u2010kappa B, Janus kinase\u2013signal transducer and activator of transcription and transforming growth factor\u2010beta pathways and the suppression of myogenesis and oxidative phosphorylation. Muscle oxidative metabolism was suppressed by both tumours and EDA2R activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study identified tumour\u2010induced transcriptional changes in muscle tissue at single\u2010nucleus resolution and highlighted the negative impact of tumours on oxidative metabolism. These findings contribute to a deeper understanding of the molecular mechanisms underlying muscle wasting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13540","type":"journal-article","created":{"date-parts":[[2024,7,13]],"date-time":"2024-07-13T03:05:46Z","timestamp":1720839946000},"page":"1898-1914","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Tumour\u2010induced alterations in single\u2010nucleus transcriptome of atrophying muscles indicate enhanced protein degradation and reduced oxidative metabolism"],"prefix":"10.1002","volume":"15","author":[{"given":"Samet","family":"Agca","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics Ko\u00e7 University  Istanbul 34450 Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aylin","family":"Domaniku\u2010Waraich","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology 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