Single-cell transcriptomics of mammalian prion diseases identifies dynamic gene signatures shared between species [mouse_scRNAseq]

Mammalian prion diseases are fatal and transmissible neurological conditions caused by the propagation of prions, self-replicating multimeric assemblies of misfolded forms of host cellular prion protein. Despite extensive studies investigating the changes in transcriptional profiles in prion diseases the mechanisms by which prion diseases induce cellular toxicity, including changes in gene expression profiles are yet to be fully characterized. Here, we took advantage of the recent developments in single-cell technologies and performed an unbiased whole-transcriptome single-nucleus transcriptomic analysis in prion disease. FVB inbred mice were intracerebrally inoculated with infectious RML brain homogenate, uninfected CD1 brain homogenate, or PBS and culled at 5 time points (20 dpi, 40 dpi , 80 dpi, 120 dpi, and when scrapie sickness was confirmed). Half brains were flash frozen and stored at -80oC until further processing. For each sample, the brain was left to thaw and a section of the frontal lobe was cut and processed for scRNA-seq using the SPLiT-seq protocol.