{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307771/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307771"],"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_1_RNA]","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":"GSE307771","cross_references":{"GSM":["GSM9230725","GSM9230724","GSM9230723","GSM9230689","GSM9230722","GSM9230729","GSM9230728","GSM9230727","GSM9230726","GSM9230691","GSM9230690","GSM9230695","GSM9230694","GSM9230693","GSM9230692","GSM9230732","GSM9230699","GSM9230698","GSM9230731","GSM9230730","GSM9230697","GSM9230696","GSM9230736","GSM9230735","GSM9230734","GSM9230733","GSM9230739","GSM9230738","GSM9230737","GSM9230743","GSM9230742","GSM9230741","GSM9230740","GSM9230703","GSM9230669","GSM9230702","GSM9230701","GSM9230668","GSM9230789","GSM9230667","GSM9230788","GSM9230700","GSM9230707","GSM9230706","GSM9230705","GSM9230704","GSM9230709","GSM9230708","GSM9230790","GSM9230673","GSM9230794","GSM9230672","GSM9230793","GSM9230792","GSM9230671","GSM9230670","GSM9230791","GSM9230798","GSM9230710","GSM9230677","GSM9230676","GSM9230797","GSM9230675","GSM9230796","GSM9230795","GSM9230674","GSM9230714","GSM9230713","GSM9230712","GSM9230679","GSM9230678","GSM9230799","GSM9230711","GSM9230718","GSM9230717","GSM9230716","GSM9230715","GSM9230719","GSM9230680","GSM9230684","GSM9230683","GSM9230682","GSM9230681","GSM9230721","GSM9230688","GSM9230687","GSM9230720","GSM9230686","GSM9230685","GSM9230648","GSM9230802","GSM9230769","GSM9230801","GSM9230647","GSM9230768","GSM9230646","GSM9230767","GSM9230800","GSM9230645","GSM9230766","GSM9230649","GSM9230803","GSM9230772","GSM9230651","GSM9230650","GSM9230771","GSM9230770","GSM9230655","GSM9230776","GSM9230775","GSM9230654","GSM9230653","GSM9230774","GSM9230652","GSM9230773","GSM9230659","GSM9230658","GSM9230779","GSM9230778","GSM9230657","GSM9230656","GSM9230777","GSM9230662","GSM9230783","GSM9230661","GSM9230782","GSM9230781","GSM9230660","GSM9230780","GSM9230666","GSM9230787","GSM9230665","GSM9230786","GSM9230664","GSM9230785","GSM9230784","GSM9230663","GSM9230747","GSM9230746","GSM9230745","GSM9230744","GSM9230749","GSM9230748","GSM9230750","GSM9230633","GSM9230754","GSM9230632","GSM9230753","GSM9230752","GSM9230631","GSM9230630","GSM9230751","GSM9230758","GSM9230637","GSM9230636","GSM9230757","GSM9230635","GSM9230756","GSM9230755","GSM9230634","GSM9230639","GSM9230638","GSM9230759","GSM9230761","GSM9230640","GSM9230760","GSM9230644","GSM9230765","GSM9230764","GSM9230643","GSM9230642","GSM9230763","GSM9230641","GSM9230762"],"GPL":["13112"],"GSE":["307771"],"taxon":["Mus musculus"],"PMID":["[42644714]"]}}