Single-nuclei RNA sequencing uncovers non-cell autonomous changes in cerebellar astrocytes and oligodendrocytes that may contribute to Spinocerebellar Ataxia Type 1 (SCA1) pathogenesis

pinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disease caused by an abnormal expansion of CAG repeats in the gene Ataxin1 (ATXN1). While mutant ATXN1 is expressed throughout the brain, SCA1 is characterized by severe degeneration of cerebellar Purkinje cells (PCs) and cerebellar gliosis. It is likely that cerebellar microenvironment and in particular glial cells contribute to the Purkinje cell specific vulnerability in SCA1. We have used single nuclei RNA sequencing (snRNA seq) to uncover effects of mutant ATXN1 on PCs gene expression changes as well as non-cell autonomous changes in glial cells transcriptomes in cerebella of Pcp2-ATXN1[82Q] mice, a transgenic SCA1 mouse model expressing mutant ATXN1 only in PCs cells