{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Tejwani L"],"funding":["National Ataxia Foundation","NIA NIH HHS","NIMH NIH HHS","NHGRI NIH HHS","NINDS NIH HHS"],"pagination":["362-383.e15"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10922326"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["112(3)"],"pubmed_abstract":["Neurodegeneration is a protracted process involving progressive changes in myriad cell types that ultimately results in the death of vulnerable neuronal populations. To dissect how individual cell types within a heterogeneous tissue contribute to the pathogenesis and progression of a neurodegenerative disorder, we performed longitudinal single-nucleus RNA sequencing of mouse and human spinocerebellar ataxia type 1 (SCA1) cerebellar tissue, establishing continuous dynamic trajectories of each cell population. Importantly, we defined the precise transcriptional changes that precede loss of Purkinje cells and, for the first time, identified robust early transcriptional dysregulation in unipolar brush cells and oligodendroglia. Finally, we applied a deep learning method to predict disease state accurately and identified specific features that enable accurate distinction of wild-type and SCA1 cells. Together, this work reveals new roles for diverse cerebellar cell types in SCA1 and provides a generalizable analysis framework for studying neurodegeneration."],"journal":["Neuron"],"pubmed_title":["Longitudinal single-cell transcriptional dynamics throughout neurodegeneration in SCA1."],"pmcid":["PMC10922326"],"funding_grant_id":["T32 NS041228","R01 AG076154","P30 AG053760","R01 NS085054","T32 NS007224","R01 NS088321","R01 HG011245","R01 AG074609","1036536","R21 MH119803","R01 NS027699","R01 AG066447","R01 NS083706"],"pubmed_authors":["Bae E","Kim K","Martuscello RT","Zhang S","Cheng Y","Shakkottai VG","Tejwani L","Yoon J","Lee C","McLoughlin HS","Ravindra NG","Wang S","Faust PL","Ni L","Ro H","Ranum LPW","Morrison LM","Luttik K","Orr HT","Zoghbi HY","van Dijk D","Nguyen B","Haidery F","Xiang Y","Grijalva RM","Lim J","Gionco J"],"additional_accession":[]},"is_claimable":false,"name":"Longitudinal single-cell transcriptional dynamics throughout neurodegeneration in SCA1.","description":"Neurodegeneration is a protracted process involving progressive changes in myriad cell types that ultimately results in the death of vulnerable neuronal populations. To dissect how individual cell types within a heterogeneous tissue contribute to the pathogenesis and progression of a neurodegenerative disorder, we performed longitudinal single-nucleus RNA sequencing of mouse and human spinocerebellar ataxia type 1 (SCA1) cerebellar tissue, establishing continuous dynamic trajectories of each cell population. Importantly, we defined the precise transcriptional changes that precede loss of Purkinje cells and, for the first time, identified robust early transcriptional dysregulation in unipolar brush cells and oligodendroglia. Finally, we applied a deep learning method to predict disease state accurately and identified specific features that enable accurate distinction of wild-type and SCA1 cells. Together, this work reveals new roles for diverse cerebellar cell types in SCA1 and provides a generalizable analysis framework for studying neurodegeneration.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2026-06-01T20:11:49.944Z","creation":"2025-04-04T00:52:04.446Z"},"accession":"S-EPMC10922326","cross_references":{"pubmed":["38016472"],"doi":["10.1016/j.neuron.2023.10.039"]}}