{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:16:55Z","timestamp":1788239815471,"version":"build-2803163510"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TH896\/7\u20131"],"award-info":[{"award-number":["TH896\/7\u20131"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>\n                    <jats:italic>COL2A1<\/jats:italic>\n                    -associated skeletal dysplasias affect cartilage extracellular matrix and endochondral growth, but patient growth-plate tissue is largely inaccessible. We generated chondrogenically induced urine-derived cells (chUDCs) from three individuals with heterozygous pathogenic\n                    <jats:italic>COL2A1<\/jats:italic>\n                    variants and three healthy controls. Classical differentiation was assessed by Alcian blue and Alizarin red staining, bulk RNA sequencing compared patient-derived and control chUDCs, and single-cell RNA sequencing was performed in two patient-derived lines.\n                    <jats:italic>COL2A1<\/jats:italic>\n                    -mutant chUDCs retained overt chondrogenic and osteogenic staining capacity without a clear patient-control separation. In contrast, bulk RNA sequencing identified a small set of consistently differential extracellular-matrix remodeling genes enriched for matrix and ossification-related programs;\n                    <jats:italic>DDR2<\/jats:italic>\n                    and\n                    <jats:italic>ADAMTS5<\/jats:italic>\n                    remained significant in leave-one-donor-out, age-adjusted and cell-composition-adjusted models. Single-cell profiling resolved multiple chUDC states, including chondrogenic, fibroblastic extracellular-matrix, IGF1R-high, and osteogenic-associated states. IGF1 co-treatment was associated with reduced osteogenic-associated module scores and increased fibroblastic\/anabolic extracellular-matrix programs. Because no IGF1-treated control-donor line was profiled, IGF1-associated changes are reported as exploratory and are not claimed to be\n                    <jats:italic>COL2A1<\/jats:italic>\n                    -specific. These findings support chUDCs as a non-invasive system for exploring selected transcriptional programs relevant to cartilage biology and growth-factor responsiveness in\n                    <jats:italic>COL2A1<\/jats:italic>\n                    -associated growth disorders.\n                  <\/jats:p>","DOI":"10.3389\/fcell.2026.1920598","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T04:26:36Z","timestamp":1788236796000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Donor-dependent heterogeneity and matrix-remodeling transcriptional programs in COL2A1-variant urine-derived cell cultures with IGF1-associated cell-state shifts"],"prefix":"10.3389","volume":"14","author":[{"given":"Alexander","family":"Schulz","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, Centre for Personalised Medicine and Research (CESAR), Friedrich-Alexander University Erlangen-N\u00fcrnberg","place":["Erlangen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Schubert","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Centre for Personalised Medicine and Research (CESAR), Friedrich-Alexander University Erlangen-N\u00fcrnberg","place":["Erlangen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily M.","family":"Brockmann","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Centre for Personalised Medicine and Research (CESAR), Friedrich-Alexander University Erlangen-N\u00fcrnberg","place":["Erlangen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arif B.","family":"Ekici","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Centre for Personalised Medicine and Research (CESAR), Friedrich-Alexander University Erlangen-N\u00fcrnberg","place":["Erlangen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Uebe","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Centre for Personalised Medicine and Research (CESAR), Friedrich-Alexander University Erlangen-N\u00fcrnberg","place":["Erlangen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian T.","family":"Thiel","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Centre for Personalised Medicine and Research (CESAR), Friedrich-Alexander University Erlangen-N\u00fcrnberg","place":["Erlangen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1302\/2058-5241.5.190088","article-title":"The growth plate: a physiologic overview","volume":"5","author":"Agirdil","year":"2020","journal-title":"EFORT Open Reviews"},{"key":"B2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1002\/humu.22915","article-title":"Mutation update for COL2A1 gene variants associated with type II collagenopathies","volume":"37","author":"Barat-Houari","year":"2016","journal-title":"Hum. 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