{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:00:15Z","timestamp":1790373615492,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2307802"],"award-info":[{"award-number":["2023YFC2307802"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2042022dx0003"],"award-info":[{"award-number":["2042022dx0003"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32525018"],"award-info":[{"award-number":["32525018"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82341023"],"award-info":[{"award-number":["82341023"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["324B2009"],"award-info":[{"award-number":["324B2009"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82401650"],"award-info":[{"award-number":["82401650"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two severe diseases sharing similar genetic, pathological, and clinical features, including TDP\u201043 pathology. However, differences in molecular changes between ALS and FTD remain elusive. Here, integrating large sets of bulk and single\u2010nucleus RNA\u2010seq from ALS\/FTD patients revealed expression and splicing changes indicating more severe oligodendrocyte damage in ALS than FTD, and more significant neuron loss in FTD. Specifically, we identified 31 oligodendrocyte\u2010specific and 507 neuron\u2010specific aberrant splicing junctions as potential biomarkers with robust classification performance, and experimentally validated a novel target in patient tissues. Moreover, we found that abnormally spliced transcripts produced de novo peptides in patients\u2019 cerebrospinal fluids. Importantly, we further identified the targets of TDP\u201043 in glial cells and decoded the differential RNA\u2010binding protein (RBP) contexts of TDP\u201043\u2010regulated aberrant splicing. These findings uncover that ALS and FTD patients have distinct dysfunctional cell populations harboring specific aberrant splicing signatures, suggesting varying cellular impacts and providing potential biomarkers and insights into molecular mechanisms underlying ALS\/FTD.<\/jats:p>","DOI":"10.1002\/advs.202514886","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T20:01:02Z","timestamp":1770235262000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aberrant Splicing Signatures Underpin Oligodendrocyte Damage in ALS and Neuron Loss in FTD"],"prefix":"10.1002","volume":"13","author":[{"given":"Chen","family":"Du","sequence":"first","affiliation":[{"name":"TaiKang Center For Life and Medical Sciences Hubei Provincial Research Center for Basic Biological Sciences Hubei Key Laboratory of Cell Homeostasis RNA Institute College of Life Sciences Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinming","family":"Li","sequence":"additional","affiliation":[{"name":"TaiKang Center For Life and Medical Sciences Hubei Provincial Research Center for Basic Biological Sciences Hubei Key Laboratory of Cell Homeostasis RNA Institute College of Life Sciences Wuhan University  Wuhan China"},{"name":"Renmin Hospital Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Physiology Pharmacology and Therapeutics Brain Science Institute Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Shen","sequence":"additional","affiliation":[{"name":"TaiKang Center For Life and Medical Sciences Hubei Provincial Research Center for Basic Biological Sciences Hubei Key Laboratory of Cell Homeostasis RNA Institute College of Life Sciences Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Yang","sequence":"additional","affiliation":[{"name":"TaiKang Center For Life and Medical Sciences Hubei Provincial Research Center for Basic Biological Sciences Hubei Key Laboratory of Cell Homeostasis RNA Institute College of Life Sciences Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Renmin Hospital Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2102-9377","authenticated-orcid":false,"given":"Yu","family":"Zhou","sequence":"additional","affiliation":[{"name":"TaiKang Center For Life and Medical Sciences Hubei Provincial Research Center for Basic Biological Sciences Hubei Key Laboratory of Cell Homeostasis RNA Institute College of Life Sciences Wuhan University  Wuhan China"},{"name":"Frontier Science Center for Immunology and Metabolism State Key Laboratory of Virology Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102011\u2010300188"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(15)00461\u20104"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr195"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.59.7.1077"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2018.10.003"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102016\u2010104271"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2013.221"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.09.066"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201035494\u2010w"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201041033\u2010y"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.02.031"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010023\u201002599\u20105"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xgen.2025.101007"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587\u2010024\u201000640\u20100"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2419818122"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abd9036"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010022\u201001205\u20103"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010023\u201002788\u20105"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adg7162"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583\u2010019\u20100152\u20102"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102021\u2010326854"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201010802\u2010z"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25975"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-021-00303-4"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201036800\u2010w"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583\u2010020\u201000415\u20107"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07456"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2023.1208876"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010cellbio\u2010100913\u2010013101"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.07.033"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aab0983"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201036585\u2010y"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.12.015"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010016\u20100144\u2010x"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010019\u20100126\u20102"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010022\u201004436\u20103"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010022\u201004424\u20107"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab702"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3462"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3454"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2013.06.016"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI139741"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471\u20104159.2005.03361.x"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(17)31287\u20104"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2023.102722"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010022\u201016772\u20105"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.136"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03253-8"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2778"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2779"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010019\u201002042\u20108"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010024\u201002705\u20101"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010021\u201000503\u2010x"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3357"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478\u2010017\u20100471\u20103"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201007042\u20107"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000013123"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty560"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010014\u20100550\u20108"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202514886","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202514886","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202514886","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:21:49Z","timestamp":1790371309000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202514886"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,4]]},"references-count":61,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/advs.202514886"],"URL":"https:\/\/doi.org\/10.1002\/advs.202514886","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,4]]},"assertion":[{"value":"2025-08-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14886"}}