{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:21:43Z","timestamp":1792797703894,"version":"4.5.0"},"reference-count":67,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["9R42AG055375\u201003"],"award-info":[{"award-number":["9R42AG055375\u201003"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To define the transcriptomic changes responsible for the histologic alterations in skeletal muscle and their progression in collagen VI\u2010related muscular dystrophy (COL6\u2010RD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>COL6\u2010RD patient muscle biopsies were stratified into three groups based on the overall level of pathologic severity considering degrees of fibrosis, muscle fiber atrophy, and fatty replacement of muscle tissue. Using microarray and RNA\u2010Seq, we then performed global gene expression profiling on the same muscle biopsies and compared their transcriptome with age\u2010 and sex\u2010matched controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>COL6\u2010RD muscle biopsy transcriptomes as a group revealed prominent upregulation of muscle extracellular matrix component genes and the downregulation of skeletal muscle and mitochondrion\u2010specific genes. Upregulation of the TGF\u03b2 pathway was the most conspicuous change across all biopsies and was fully evident even in the mildest\/earliest histological group. There was no difference in the overall transcriptional signature between the different histologic groups but polyserial analysis identified relative changes along with COL6\u2010RD histological severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Overall, our study establishes the prominent dysregulation of extracellular matrix genes, TGF\u03b2 signaling, and its downstream cellular pathways at the transcriptomic level in COL6\u2010RD muscle.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51450","type":"journal-article","created":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T06:49:40Z","timestamp":1635922180000},"page":"2184-2198","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Transcriptome analysis of collagen VI\u2010related muscular dystrophy muscle biopsies"],"prefix":"10.1002","volume":"8","author":[{"given":"Eleonora","family":"Guadagnin","sequence":"first","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section National Institute of Neurological Disorders and Stroke National Institutes of Health 35 Convent Drive, BLDG 35 RM 2A116 Bethesda Maryland 20892 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5313-9514","authenticated-orcid":false,"given":"Payam","family":"Mohassel","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section National Institute of Neurological Disorders and Stroke National Institutes of Health 35 Convent Drive, BLDG 35 RM 2A116 Bethesda Maryland 20892 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kory R.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Bioinformatics Section Intramural Information Technology &amp; Bioinformatics Program National Institute of Neurological Disorders and Stroke National Institutes of Health 10 Center Drive, BG 10 RM 5S223 Bethesda Maryland 20892 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Biomedical Informatics Department of Biomedical Engineering University of Florida 1064 Center Drive, NEB 364 Gainsville Florida 32611 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariarita","family":"Santi","sequence":"additional","affiliation":[{"name":"Department of Pathology Children\u2019s Hospital of Philadelphia 324 South 34<sup>th<\/sup> Street Philadelphia Pennsylvania 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prech","family":"Uapinyoying","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section National Institute of Neurological Disorders and Stroke National Institutes of Health 35 Convent Drive, BLDG 35 RM 2A116 Bethesda Maryland 20892 USA"},{"name":"Center for Genetic Medicine Research Children's Research Institute Children's National Health System Washington DC 20010 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jahannaz","family":"Dastgir","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section National Institute of Neurological Disorders and Stroke National Institutes of Health 35 Convent Drive, BLDG 35 RM 2A116 Bethesda Maryland 20892 USA"},{"name":"Atlantic Health System Goryeb Children\u2019s Hospital Morristown New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Hu","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section National Institute of Neurological Disorders and Stroke National Institutes of Health 35 Convent Drive, BLDG 35 RM 2A116 Bethesda Maryland 20892 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allissa","family":"Dillmann","sequence":"additional","affiliation":[{"name":"Cell Biology and Gene Expression Section Laboratory of Neurogenetics National Institute of Aging National Institutes of Health 35 Convent Drive, BG 35 RM 1A116 Bethesda Maryland 20892 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Cookson","sequence":"additional","affiliation":[{"name":"Cell Biology and Gene Expression Section Laboratory of Neurogenetics National Institute of Aging National Institutes of Health 35 Convent Drive, BG 35 RM 1A116 Bethesda Maryland 20892 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2168-1119","authenticated-orcid":false,"given":"A. Reghan","family":"Foley","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section National Institute of Neurological Disorders and Stroke National Institutes of Health 35 Convent Drive, BLDG 35 RM 2A116 Bethesda Maryland 20892 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten G.","family":"B\u00f6nnemann","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section National Institute of Neurological Disorders and Stroke National Institutes of Health 35 Convent Drive, BLDG 35 RM 2A116 Bethesda Maryland 20892 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.121027598"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2011.81"},{"key":"e_1_2_8_4_1","volume-title":"GeneReviews\u00ae [Internet]","author":"Foley AR","year":"1993"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.21088"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/nen.0b013e3181634ef7"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201057110\u20106"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2017.12.008"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1086\/340608"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/377107"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi025"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20704"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22429"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2018.06.005"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0077430"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0145107"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.175927"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0189664"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022\u2010510X(88)90227\u20104"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn923"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1270"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0800962105"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2247"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2964"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1053\/ejpn.2002.0618"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960\u20108966(03)00091\u20109"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2005.01.004"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102164\u201015\u2010912"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132532"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-417028-5.00006-5"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2011.0307"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523\u20101747.ep12363389"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000173836.09176.c4"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/965631"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.192571199"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06\u20107285com"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960\u20108966(02)00093\u20107"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh635"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003750"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.05.004"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100625200"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20740"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1177\/03635465010290040201"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300250"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2016.09.079"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2001.280.6.L1327"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1997.3858"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2005.03.024"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.36.23463"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529\u20100131(200012)43:12<2703:AID\u2010ANR10>3.0.CO;2\u2010Y"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.12.159"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021\u20109258(18)77221\u20109"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021\u20109258(18)37912\u20102"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/386078a0"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700667"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2006.11.017"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e09-09-0812"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2014.11.011"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.132563"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/scrt411"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M801166200"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11\u2010190728"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2014.02.003"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.050"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.17589"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.131.4.1083"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0078644"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51450","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acn3.51450","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51450","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T11:18:00Z","timestamp":1692789480000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.51450"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11]]},"references-count":67,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.1002\/acn3.51450"],"URL":"https:\/\/doi.org\/10.1002\/acn3.51450","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11]]},"assertion":[{"value":"2021-05-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}