GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307772/primaryOK200OtherMus musculusOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307772GEOGSEfalseDecoding neuronal vulnerability: multidimensional analysis of D1R- and D2R- medium-sized spiny neurons in Huntington's disease [Dataset_2_gDNA]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