{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:38:51Z","timestamp":1790707131162,"version":"4.1.0"},"reference-count":68,"publisher":"American Society for Clinical Investigation","issue":"13","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":43,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["1R21AR079033"],"award-info":[{"award-number":["1R21AR079033"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["1R21AR078400"],"award-info":[{"award-number":["1R21AR078400"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:p>\n                    We previously identified a muscular dystrophy caused by biallelic variants in\n                    <jats:italic>JAGGED2<\/jats:italic>\n                    (\n                    <jats:italic>JAG2<\/jats:italic>\n                    ), whose protein product, JAG2, is a canonical NOTCH ligand. However, the disease mechanism remains unclear, particularly with respect to muscle stem cell (muscle satellite cell\/MuSC) function and muscle regeneration. We examined the consequences of\n                    <jats:italic>JAG2<\/jats:italic>\n                    deficiency and modeled pathogenic\n                    <jats:italic>JAG2<\/jats:italic>\n                    variants in vitro and in vivo, the latter in mouse and fly models and with particular attention to the MuSC\u2013muscle endothelial cell (MuEC) niche. We found that both\n                    <jats:italic>Jag2<\/jats:italic>\n                    deficiency and overexpression of pathogenic\n                    <jats:italic>JAG2<\/jats:italic>\n                    variants impaired NOTCH signaling and myogenic self-renewal and differentiation. Hypomorphic\n                    <jats:italic>Jag2<\/jats:italic>\n                    mutant (\n                    <jats:italic>\n                      Jag2\n                      <jats:sup>sm<\/jats:sup>\n                    <\/jats:italic>\n                    ) mice displayed depleted MuSCs, corresponding with impaired muscle regeneration in those mice. Coculture experiments and the examination of cell type\u2013specific\n                    <jats:italic>Jag2<\/jats:italic>\n                    conditional knockout mice demonstrated that MuEC-specific\n                    <jats:italic>Jag2<\/jats:italic>\n                    knockout resulted in reduced MuSC self-renewal, while MuSC-specific\n                    <jats:italic>Jag2<\/jats:italic>\n                    knockout resulted in reduced myogenic differentiation. Human reference\n                    <jats:italic>JAG2<\/jats:italic>\n                    , but not human pathogenic variants of\n                    <jats:italic>JAG2<\/jats:italic>\n                    , rescued the deficiency of\n                    <jats:italic>Serrate<\/jats:italic>\n                    , the\n                    <jats:italic>Drosophila<\/jats:italic>\n                    ortholog of\n                    <jats:italic>JAG2<\/jats:italic>\n                    . Therefore, pathogenic variants in\n                    <jats:italic>JAG2<\/jats:italic>\n                    impair muscle development and regeneration through disrupted cell-autonomous\n                    <jats:italic>cis-<\/jats:italic>\n                    inhibition and nonautonomous\n                    <jats:italic>trans-<\/jats:italic>\n                    activation involving NOTCH signaling dysfunction. Our findings indicate that optimizing JAG2-mediated NOTCH signaling is a potential therapeutic approach for\n                    <jats:italic>JAG2<\/jats:italic>\n                    -related muscular dystrophy.\n                  <\/jats:p>","DOI":"10.1172\/jci198639","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T16:00:19Z","timestamp":1779206419000},"source":"Crossref","is-referenced-by-count":5,"title":["Deficiency of muscular dystrophy\u2013related gene JAG2 causes NOTCH signaling dysfunction in muscle stem cells"],"prefix":"10.1172","volume":"136","author":[{"given":"Minoru","family":"Tanaka","sequence":"first","affiliation":[{"name":"Stem Cell Institute and"},{"name":"Greg Marzolf Jr. Muscular Dystrophy Center and Department of Neurology, University of Minnesota Medical School, Minneapolis, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nam 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