Multi-omic profiling reveals the ataxia protein sacsin is required for integrin trafficking and synaptic organization

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a childhood-onset cerebellar ataxia caused by mutations in SACS, which encodes the protein sacsin. Cellular ARSACS phenotypes include mitochondrial dysfunction, intermediate filament disorganization, and the progressive death of cerebellar Purkinje neurons. It is unclear how the loss of sacsin function causes these deficits, or why they manifest as cerebellar ataxia. To investigate this, we performed multi-omic profiling of sacsin knockout cells and compared them to wild-type controls We generated an SH-SY5Y cell line by CRISPR/Cas9 genome editing that do not express sacsin. The transcriptomes of these sacsin KO cells was then compared with WT controls by RNASeq. Both KO and WT cells underwent neuronal differentiation before RNA extraction and we used three replicates per group.