Cell-Type-Specific Gene Expression Profiling in Adult Mouse Brain Reveals Normal and Disease-State Signatures

摘要

The role of brain cell-type-specific functions andprofiles in pathological and non-pathological contextsis still poorly defined. Such cell-type-specific geneexpression profiles in solid, adult tissues wouldbenefit from approaches that avoid cellular stress duringisolation. Here, we developed such an approachand identified highly selective transcriptomic signaturesin adult mouse striatal direct and indirect spinyprojection neurons, astrocytes, and microglia. Integratingtranscriptomic and epigenetic data, we obtaineda comprehensive model for cell-type-specificregulation of gene expression in the mouse striatum.A cross-analysis with transcriptomic and epigenomicdata generated from mouse and human Huntington’sdisease (HD) brains shows that opposite epigeneticmechanisms govern the transcriptional regulation ofstriatal neurons and glial cells and may contribute topathogenic and compensatory mechanisms. Overall,these data validate this less stressful method for theinvestigation of cellular specificity in the adult mousebrain and demonstrate the potential of integrativestudies using multiple databases.