{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307772/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Mus musculus"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307772"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Decoding neuronal vulnerability: multidimensional analysis of D1R- and D2R- medium-sized spiny neurons in Huntington's disease [Dataset_2_gDNA]","description":"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.","dates":{"publication":"2026/08/31"},"accession":"GSE307772","cross_references":{"GSM":["GSM9230846","GSM9230967","GSM9230845","GSM9230966","GSM9230965","GSM9230844","GSM9230843","GSM9230964","GSM9230849","GSM9230848","GSM9230969","GSM9230968","GSM9230847","GSM9230970","GSM9230974","GSM9230853","GSM9230973","GSM9230852","GSM9230851","GSM9230972","GSM9230971","GSM9230850","GSM9230857","GSM9230978","GSM9230977","GSM9230856","GSM9230976","GSM9230855","GSM9230854","GSM9230975","GSM9230859","GSM9230979","GSM9230858","GSM9230860","GSM9230981","GSM9230980","GSM9230985","GSM9230864","GSM9230863","GSM9230984","GSM9230862","GSM9230983","GSM9230861","GSM9230982","GSM9230945","GSM9230824","GSM9230944","GSM9230823","GSM9230822","GSM9230943","GSM9230942","GSM9230821","GSM9230828","GSM9230949","GSM9230948","GSM9230827","GSM9230826","GSM9230947","GSM9230825","GSM9230946","GSM9230829","GSM9230831","GSM9230952","GSM9230951","GSM9230830","GSM9230950","GSM9230835","GSM9230956","GSM9230834","GSM9230955","GSM9230954","GSM9230833","GSM9230832","GSM9230953","GSM9230839","GSM9230838","GSM9230959","GSM9230837","GSM9230958","GSM9230957","GSM9230836","GSM9230842","GSM9230963","GSM9230841","GSM9230962","GSM9230840","GSM9230961","GSM9230960","GSM9230923","GSM9230922","GSM9230889","GSM9230888","GSM9230921","GSM9230920","GSM9230887","GSM9230806","GSM9230927","GSM9230805","GSM9230926","GSM9230925","GSM9230804","GSM9230924","GSM9230809","GSM9230808","GSM9230929","GSM9230928","GSM9230807","GSM9230893","GSM9230892","GSM9230891","GSM9230890","GSM9230897","GSM9230930","GSM9230896","GSM9230895","GSM9230894","GSM9230934","GSM9230813","GSM9230812","GSM9230933","GSM9230811","GSM9230899","GSM9230932","GSM9230931","GSM9230898","GSM9230810","GSM9230817","GSM9230938","GSM9230937","GSM9230816","GSM9230815","GSM9230936","GSM9230814","GSM9230935","GSM9230819","GSM9230818","GSM9230939","GSM9230941","GSM9230820","GSM9230940","GSM9230868","GSM9230989","GSM9230901","GSM9230988","GSM9230867","GSM9230900","GSM9230866","GSM9230987","GSM9230986","GSM9230865","GSM9230905","GSM9230904","GSM9230903","GSM9230902","GSM9230869","GSM9230909","GSM9230908","GSM9230907","GSM9230906","GSM9230871","GSM9230992","GSM9230991","GSM9230870","GSM9230990","GSM9230875","GSM9230995","GSM9230874","GSM9230994","GSM9230873","GSM9230872","GSM9230993","GSM9230879","GSM9230912","GSM9230911","GSM9230878","GSM9230877","GSM9230910","GSM9230876","GSM9230916","GSM9230915","GSM9230914","GSM9230913","GSM9230919","GSM9230918","GSM9230917","GSM9230882","GSM9230881","GSM9230880","GSM9230886","GSM9230885","GSM9230884","GSM9230883"],"GPL":["13112"],"GSE":["307772"],"taxon":["Mus musculus"],"PMID":["[42644714]"]}}