{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T04:16:00Z","timestamp":1791778560541,"version":"4.3.4"},"reference-count":44,"publisher":"American Society for Clinical Investigation","issue":"13","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NIH NIAMS T32 AR065972,R01NS120060,R01NS117912,P50 AR052646"],"award-info":[{"award-number":["NIH NIAMS T32 AR065972,R01NS120060,R01NS117912,P50 AR052646"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"U.S. Department of Defense","award":["DOD MD190060"],"award-info":[{"award-number":["DOD MD190060"]}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"crossref","award":["GT11023"],"award-info":[{"award-number":["GT11023"]}],"id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005693","name":"Parent Project Muscular Dystrophy","doi-asserted-by":"crossref","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100005693","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,8]]},"abstract":"<jats:p>\n                    Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disorder involving cycles of muscle degeneration and regeneration, leading to accumulation of intramuscular fibrosis and fat. Ablation of Osteopontin\/\n                    <jats:italic>Spp1<\/jats:italic>\n                    in a murine model of DMD (\n                    <jats:italic>mdx<\/jats:italic>\n                    ) improves the dystrophic phenotype, but the source of Spp1 and its impact on target cells in dystrophic muscles remain unknown. In dystrophic muscles, macrophages are the predominate infiltrating leukocyte and express high levels of Spp1. We used macrophage-specific ablation combined with single-cell transcriptional profiling to uncover the impact of macrophage-derived Spp1 on cell-cell interactions in\n                    <jats:italic>mdx<\/jats:italic>\n                    muscles. Ablation of macrophage-specific\n                    <jats:italic>Spp1<\/jats:italic>\n                    (\n                    <jats:italic>cKO<\/jats:italic>\n                    ) correlated with reduction of 2 PDGFRa\n                    <jats:sup>+<\/jats:sup>\n                    stromal cell populations, expressing\n                    <jats:italic>\n                      Lifr\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:italic>\n                    and\n                    <jats:italic>\n                      Procr\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:italic>\n                    . Sorting and transcriptional profiling of these populations confirmed that they are enriched in adipogenesis genes and are highly related to fibroadipogenic precursors (FAPS). These adipogenic stromal cells (ASC) displayed more adipogenic potential in vitro compared with FAPS, likely due to a more differentiated state. Reduction of ASCs correlated with reduced intramuscular diaphragmatic fat and improved diaphragm function. These data suggest a role for myeloid-derived Spp1 in the differentiation of stromal cells towards an adipogenic fate, leading to accumulation of intramuscular fat in dystrophic muscles.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.181946","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T14:00:32Z","timestamp":1751896832000},"source":"Crossref","is-referenced-by-count":15,"title":["Macrophage-derived Spp1 promotes intramuscular fat in dystrophic muscle"],"prefix":"10.1172","volume":"10","author":[{"given":"Philip K.","family":"Farahat","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics,"},{"name":"Muscle Biology and Disease Research Center, and"},{"name":"Institute for Immunology, University of California, Irvine, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chino","family":"Kumagai-Cresse","sequence":"additional","affiliation":[{"name":"Department of 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