Browsing School, Graduate by Subject "eccentric spiny neurons"
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Bioinformatic Analysis of Single Nucleus Transcriptome Data of Huntington's DiseaseHuntington’s Disease (HD) is a dominantly inherited neurodegenerative disorder caused by a trinucleotide expansion in exon 1 of the Huntingtin (Htt) gene. The earliest changes in HD are observed in the striatum, prior to the onset of symptoms. Here we use a knock in HttQ175/+ mouse model to perform single nucleus RNA sequencing (snRNAseq) of the striatums of four HttQ175/+ and three wild type 14 and 15 month old mice and obtain their expression profiles. Using available snRNAseq quality control and analysis methods, we identify eleven cell types within our samples, including the newly discovered “Eccentric MSNs”. We compute the differentially expressed genes between the two genotypes and find significant lowering of cell type specific markers in most cells with the HttQ175/+ mutation. Trajectory analyses reveal stages of HttQ175/+ MSNs that range from identical to extremely distinguished form the wild type MSNs, supporting the length dependent somatic expansion hypothesis.