{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:53:07Z","timestamp":1791287587515,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,7,12]],"date-time":"2023-07-12T00:00:00Z","timestamp":1689120000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2023,7,12]],"date-time":"2023-07-12T00:00:00Z","timestamp":1689120000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005825","name":"National Institute of Food and Agriculture","doi-asserted-by":"publisher","award":["2020\u201067015\u201030823"],"award-info":[{"award-number":["2020\u201067015\u201030823"]}],"id":[{"id":"10.13039\/100005825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F31AR077424"],"award-info":[{"award-number":["F31AR077424"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AR078695"],"award-info":[{"award-number":["R01AR078695"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL157519"],"award-info":[{"award-number":["R01HL157519"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM130555"],"award-info":[{"award-number":["P20GM130555"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R15DK122383"],"award-info":[{"award-number":["R15DK122383"]}],"id":[{"id":"10.13039\/100000002","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":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Intramuscular fat (IMF) and intramuscular connective tissue (IMC) are often seen in human myopathies and are central to beef quality. The mechanisms regulating their accumulation remain poorly understood. Here, we explored the possibility of using beef cattle as a novel model for mechanistic studies of intramuscular adipogenesis and fibrogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Skeletal muscle single\u2010cell RNAseq was performed on three cattle breeds, including Wagyu (high IMF), Brahman (abundant IMC but scarce IMF), and Wagyu\/Brahman cross. Sophisticated bioinformatics analyses, including clustering analysis, gene set enrichment analyses, gene regulatory network construction, RNA velocity, pseudotime analysis, and cell\u2013cell communication analysis, were performed to elucidate heterogeneities and differentiation processes of individual cell types and differences between cattle breeds. Experiments were conducted to validate the function and specificity of identified key regulatory and marker genes. Integrated analysis with multiple published human and non\u2010human primate datasets was performed to identify common mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 32\u00a0708 cells and 21 clusters were identified, including fibro\/adipogenic progenitor (FAP) and other resident and infiltrating cell types. We identified an endomysial adipogenic FAP subpopulation enriched for\n                      <jats:italic>COL4A1<\/jats:italic>\n                      and\n                      <jats:italic>CFD<\/jats:italic>\n                      (log2FC\u00a0=\u00a03.19 and 1.92, respectively;\n                      <jats:italic>P\u00a0&lt;<\/jats:italic>\n                      \u00a00.0001) and a perimysial fibrogenic FAP subpopulation enriched for\n                      <jats:italic>COL1A1<\/jats:italic>\n                      and\n                      <jats:italic>POSTN<\/jats:italic>\n                      (log2FC\u00a0=\u00a01.83 and 0.87, respectively;\n                      <jats:italic>P\u00a0&lt;<\/jats:italic>\n                      \u00a00.0001), both of which were likely derived from an unspecified subpopulation. Further analysis revealed more progressed adipogenic programming of Wagyu FAPs and more advanced fibrogenic programming of Brahman FAPs. Mechanistically, NAB2 drives\n                      <jats:italic>CFD<\/jats:italic>\n                      expression, which in turn promotes adipogenesis.\n                      <jats:italic>CFD<\/jats:italic>\n                      expression in FAPs of young cattle before the onset of intramuscular adipogenesis was predictive of IMF contents in adulthood (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a00.885,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.01). Similar adipogenic and fibrogenic FAPs were identified in humans and monkeys. In aged humans with metabolic syndrome and progressed Duchenne muscular dystrophy (DMD) patients, increased\n                      <jats:italic>CFD<\/jats:italic>\n                      expression was observed (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05 and\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001, respectively), which was positively correlated with adipogenic marker expression, including\n                      <jats:italic>ADIPOQ<\/jats:italic>\n                      (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a00.303,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.01; and\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a00.348,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.01, respectively). The specificity of\n                      <jats:italic>Postn\/POSTN<\/jats:italic>\n                      as a fibrogenic FAP marker was validated using a lineage\u2010tracing mouse line.\n                      <jats:italic>POSTN<\/jats:italic>\n                      expression was elevated in Brahman FAPs (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001) and DMD patients (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.01) but not in aged humans. Strong interactions between vascular cells and FAPs were also identified.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our study demonstrates the feasibility of beef cattle as a model for studying IMF and IMC. We illustrate the FAP programming during intramuscular adipogenesis and fibrogenesis and reveal the reliability of\n                      <jats:italic>CFD<\/jats:italic>\n                      as a predictor and biomarker of IMF accumulation in cattle and humans.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13292","type":"journal-article","created":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T02:51:25Z","timestamp":1689216685000},"page":"2152-2167","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["A single\u2010cell atlas of bovine skeletal muscle reveals mechanisms regulating intramuscular adipogenesis and fibrogenesis"],"prefix":"10.1002","volume":"14","author":[{"given":"Leshan","family":"Wang","sequence":"first","affiliation":[{"name":"School of Animal Science Louisiana State University Agricultural Center  Baton Rouge LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peidong","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Animal Science Louisiana State University Agricultural Center  Baton Rouge LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyang","family":"Li","sequence":"additional","affiliation":[{"name":"School of Animal Science Louisiana State University Agricultural Center  Baton Rouge LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianglin","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Animal Science Louisiana State University Agricultural Center  Baton Rouge LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyang","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Computer Science Old Dominion University  Norfolk VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxia","family":"Li","sequence":"additional","affiliation":[{"name":"School of Animal Science Louisiana State University Agricultural Center  Baton Rouge LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xujia","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Animal Science Louisiana State University Agricultural Center  Baton Rouge LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangwen","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Computer Science Old Dominion University  Norfolk VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantine","family":"Simintiras","sequence":"additional","affiliation":[{"name":"School of Animal Science Louisiana State University Agricultural Center  Baton Rouge LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Welborn","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine Louisiana State University  Baton Rouge LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"McMillin","sequence":"additional","affiliation":[{"name":"School of Animal Science Louisiana State University Agricultural Center  Baton Rouge LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Oprescu","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences Purdue University  West Lafayette IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihuan","family":"Kuang","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences Purdue University  West Lafayette IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5419-2691","authenticated-orcid":false,"given":"Xing","family":"Fu","sequence":"additional","affiliation":[{"name":"School of Animal Science Louisiana State University Agricultural Center  Baton Rouge LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2015.0365"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2015.01.003"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.043562"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.meatsci.2013.05.040"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.2527\/jas2017.2022"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.02.026"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32239"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3990"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a004978"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2008.01.005"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0953-816x.2001.01596.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2014.11.003"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200212000-00010"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200502101"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201439195"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-1317"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16427"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.01904"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1549-8719.2010.00036.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000047867.98019.2D"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/10739680590904955"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01790"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M067207"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.01.051"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/7840652"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/09168451.2018.1559719"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.11.017"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62263-8"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2013.08.001"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0323"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22084205"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13395-015-0059-1"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-7285com"},{"key":"e_1_2_7_35_1","first-page":"184","article-title":"The role of fibrosis in Duchenne muscular dystrophy","volume":"31","author":"Klingler W","year":"2012","journal-title":"Acta Myol"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes12081107"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3299706"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.06.005"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0117835"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.69209"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12899"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.13292","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.13292","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T21:45:14Z","timestamp":1697147114000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.13292"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,12]]},"references-count":40,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["10.1002\/jcsm.13292"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.13292","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,12]]},"assertion":[{"value":"2022-11-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}