{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:01:31Z","timestamp":1789041691876,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"13-14","license":[{"start":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:00:00Z","timestamp":1620777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN\u20102014\u201004810"],"award-info":[{"award-number":["RGPIN\u20102014\u201004810"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN\u20102019\u201004786"],"award-info":[{"award-number":["RGPIN\u20102019\u201004786"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN\u20102020\u201005099"],"award-info":[{"award-number":["RGPIN\u20102020\u201005099"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN\u20102014\u201004810"],"award-info":[{"award-number":["RGPIN\u20102014\u201004810"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN\u20102019\u201004786"],"award-info":[{"award-number":["RGPIN\u20102019\u201004786"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Spinal muscular atrophy (SMA) is an autosomal recessive disorder that represents a significant cause of infant mortality. SMA is characterized by reduced levels of the Survival Motor Neuron protein leading to the loss of alpha motor neurons in the spinal cord and brain stem as well as defects in peripheral tissues such as skeletal muscle and liver. With progress in promising therapies such as antisense oligonucleotide and gene replacement, there remains a need to better understand disease subtypes and develop biomarkers for improved diagnostics and therapeutic monitoring. In this study, we have examined the utility of extracellular vesicles as a source of biomarker discovery in patient\u2010derived fibroblast cells. Proteome examination utilizing data\u2010independent acquisition and ion mobility mass spectrometry identified 684 protein groups present in all biological replicates tested. Label\u2010free quantitative analysis identified 116 statistically significant protein alterations compared to control cells, including several known SMA biomarkers. Protein level differences were also observed in regulators of Wnt signaling and Cajal bodies. Finally, levels of insulin growth factor binding protein\u20103 were validated as being significantly higher in extracellular vesicles isolated from SMA cells. We conclude that extracellular vesicles represent a promising source for SMA biomarker discovery as well as a relevant constituent for advancing our understanding of SMA pathophysiology.<\/jats:p>","DOI":"10.1002\/pmic.202000301","type":"journal-article","created":{"date-parts":[[2021,4,24]],"date-time":"2021-04-24T07:54:58Z","timestamp":1619250898000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Label\u2010free quantitative proteomic analysis of extracellular vesicles released from fibroblasts derived from patients with spinal muscular atrophy"],"prefix":"10.1002","volume":"21","author":[{"given":"Justin","family":"Roberto","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Windsor  Windsor Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy L.","family":"Poulin","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Program Ottawa Hospital Research Institute  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin J.","family":"Parks","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Program Ottawa Hospital Research Institute  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2485-3505","authenticated-orcid":false,"given":"Panayiotis O.","family":"Vacratsis","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Windsor  Windsor Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00898"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-002-0828-x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/3030"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.117.4.1100"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90460-3"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-018-2849-1"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)48095-7"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201100477"},{"key":"e_1_2_8_10_1","first-page":"144","article-title":"Absolute quantification of proteins by LCMSE: A virtue of parallel MS acquisition","volume":"5","author":"Silva J. C.","year":"2006","journal-title":"Molecular Cell"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euprot.2014.02.001"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-74346-9"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0167087"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M114.041038"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053728"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035462"},{"key":"e_1_2_8_17_1","first-page":"22","volume":"32","author":"Li D. K.","year":"2014","journal-title":"Cell & Developmental Biology"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1155085"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.89970"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.236"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2018.00010"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1179\/1743132812Y.0000000027"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz195"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.090183"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02677"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201600144"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.908401"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-012-0921-8"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12192-012-0357-z"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.10.059"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/gm498"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3349\/ymj.2020.61.4.273"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku484"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.4103\/1735-5362.235160"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/17482960802160370"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)48458-X"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00117"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10485"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2012.00056"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-7-14"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000353"},{"key":"e_1_2_8_42_1","first-page":"4061","volume":"27","author":"Wan B.","year":"2018","journal-title":"Human Molecular Genetics"}],"container-title":["PROTEOMICS"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pmic.202000301","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pmic.202000301","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pmic.202000301","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T10:48:55Z","timestamp":1761043735000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/pmic.202000301"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,12]]},"references-count":41,"journal-issue":{"issue":"13-14","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1002\/pmic.202000301"],"URL":"https:\/\/doi.org\/10.1002\/pmic.202000301","archive":["Portico"],"relation":{},"ISSN":["1615-9853","1615-9861"],"issn-type":[{"value":"1615-9853","type":"print"},{"value":"1615-9861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,12]]},"assertion":[{"value":"2020-11-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2000301"}}