GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307771/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307771GEOGSEfalseDecoding neuronal vulnerability: multidimensional analysis of D1R- and D2R- medium-sized spiny neurons in Huntington's disease [Dataset_1_RNA]Understanding the molecular mechanisms driving selective neuronal vulnerability to different neurodegenerative disorders remains a crucial, but unsolved question. Here we explored the case of Huntington's disease (HD), where the striatum and, specifically, dopamine receptor 1 (D1R) and dopamine receptor 2 (D2R) medium-sized spiny neurons (MSNs), exhibit differential susceptibility to the HTT CAG-repeat expansion mutation, with D2R-neurons being impacted earlier and more significantly. To unravel differences between D2R and D1R MSNs, we employed a multidimensional approach, integrating genomic, transcriptional, morphological, and somatic instability analyses. Specifically, we used Htt CAG knock-in mouse models harboring 18 (HttQ20: “control”) or ~190 (HttQ175: “HD”) consecutive CAG repeats, expressing tdTomato and EGFP under the control of Drd1 and Drd2 promoters, respectively. First, comprehensive genomic and transcriptomic analyses following fluorescence-activated cell sorting of dissociated striatal neurons, revealed no large copy number variations, but distinct gene expression profiles, indicating a significant upregulation of oxidative phosphorylation and translation pathways in D1R positive neurons at pre-symptomatic stage. Secondly, morphological analyses revealed a greater proportion of D1R-positive neurons compared to D2R-positive neurons in HD mice, particularly in the ventral-medial striatum, with D2R-positive neurons presenting an increased nuclear accumulation of mutant huntingtin aggregates. In summary, our integrative study suggests that the distinct vulnerability of MSNs in HD might result from a combination of an early transcriptional compensatory/buffering-response of D1R neurons together with specific susceptibility of D2R neurons.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 musculus