New Method for Cell-type specific gene expression profiling in adult mouse brain reveals normal and disease-state signatures. Mus Musculus

The role of brain cell-type-specific functions and profiles in pathological and non-pathological contexts are still poorly defined. Such cell-type-specific gene expression profile in solid, adult tissues would benefit from approaches that avoid cellular stress during isolation. Here, we developed a new approach for the gene expression profiling of brain cell populations. We identified highly selective transcriptomic signatures in adult mouse striatal direct and indirect spiny projection neurons, astrocytes, and microglia. Integrating transcriptomic and epigenetic data, we obtained a comprehensive model for cell-type-specific regulation of gene expression in the mouse striatum. A cross-analysis with transcriptomic and epigenomic data generated from mouse and human Huntington's disease (HD) brains show that opposite epigenetic mechanisms govern the transcriptional regulation of striatal neurons and glial cells and may contribute to pathogenic and compensatory mechanisms. Overall, these data validate this stress-free method for the investigation of cellular specificity in the adult mouse brain and demonstrate the strong potential of integrative studies using multiple databases.