GSE171099 Impaired inhibitory GABAergic synaptic transmission and transcription studied in single neurons by Patch-seq in Huntington ’s disease

Contributors : Foteini Paraskevopoulou ; Poorya Parvizi ; G ökçe Senger ; Nurcan Tuncbag ; Christian Rosenmund ; Ferah YildirimSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusTranscriptional dysregulation in Huntington ’s disease (HD) causes functional deficits in striatal neurons. Here, we performed Patch-seq in an in vitro HD model to investigate the effects of mutant huntingtin (Htt) on synaptic transmission and gene transcription in single striatal neurons. We found that expression of mutant Htt decreased th e synaptic output of striatal neurons in a cell autonomous fashion and identified a number of genes, whose dysregulation was correlated with physiological deficiencies in mutant Htt neurons. In support of a pivotal role for epigenetic mechanisms in HD pathophysiology, we found that inhibiting histon e deacetylase 1/3 activities rectified several functional and morphological deficits and alleviated the aberrant transcriptional profiles in mutant Htt neurons. With this study, we demonstrate that Patch-seq technology can be applied both to better understand molecular mechanisms underlying a comple x neurological disease at single-cell level and to provide a platform for screening for therapeutics for the disease.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research