GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE333nnn/GSE333370/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE333370GEOGSEfalseLoss of striatal astrocyte u-crystallin (Crym) contributes to early stage Huntington’s disease pathophysiologyAstrocytes display regional heterogeneity in the brain, underscoring the need to study defined populations. A striatal astrocyte subpopulation expressing  crystallin (gene: Crym) regulates perseverative behaviors, but its role in disease is unclear. We found that astrocytic Crym and  crystallin protein expression levels are reduced significantly in human Huntington’s disease (HD) tissue and cerebrospinal fluid, and in HD mouse models. Selective astrocytic  crystallin restoration in R6/2 HD model mice improved astrocyte and neuronal morphology, electrophysiology, gene expression, and improved early stage cognitive and compulsive behaviors, though late stage motor deficits remained mostly unchanged. Approximately 32% of the  crystallin rescued astrocytic genes overlapped with those dysregulated in human HD, indicating conserved molecular corrections. These results identify  crystallin expressing astrocytes as modulators of HD pathophysiology and suggest that restoring  crystallin could be beneficial in early disease stages. The findings highlight the importance of identifying specific astrocyte subpopulations to understand and potentially treat brain disorders.2026/09/28GSE333370GSM9761594GSM9761583GSM9761595GSM9761584GSM9761592GSM9761593GSM9761582GSM9761590GSM9761591GSM9761589GSM9761587GSM9761588GSM9761596GSM9761585GSM9761586GSM976159721103333370Mus musculus