Combined Analysis of mRNA Expression and Open Chromatin in Microglia

The advance of single-cell RNA-sequencing technologies in the past years has enabled unprecedented insights into the complexity and heterogeneity of microglial cell states in the homeostatic and diseased brainBrain. This includes rather complex proteomic, metabolomic, morphological, transcriptomicTranscriptomics, and epigeneticEpigenetics adaptations to external stimuli and challenges resulting in a novel concept of core microgliaMicroglia properties and functions. To uncover the regulatory programs facilitating the rapid transcriptomicTranscriptomics adaptation in response to changes in the local microenvironment, the accessibility of gene bodies and gene regulatory elements can be assessed. Here, we describe the application of a previously published method for simultaneous high-throughput ATAC and RNA expression with sequencing (SHARE-seq) on microgliaMicroglia nuclei isolated from frozen mouse brainBrain tissue.