Longitudinal single-cell transcriptional dynamics throughout neurodegeneration in SCA1.

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 stat

SUBMITTER: Tejwani L 

PROVIDER: S-EPMC10922326 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature