GSE123328
Open chromatin landscape of rat microglia upon inflammatory or pro-invasive polarization
Microglia are brain-resident, myeloid cells that play important roles in health and brain pathologies. While data on chromatin accessibility in activated murine microglia are available, there is no such data on rat microglia subjected to different stimuli. Herein, we report a comprehensive, replicated, FDR-controlled dataset of DNase-hypersensitive (DHS) open chromatin regions for the rat microglia. We compared open chromatin landscapes in untreated primary microglial cultures and cultures stimulated for 6h with either lipopolysaccharide (LPS) or glioma-conditioned medium (GCM). Glioma-secreted factors induce the pro-invasive and immunosuppressive activation of microglia, in which these cells promote tumor growth. The open chromatin landscape of the rat microglia consisted of 126,640 reproducible DHS regions, of which 12,357 and 2,303 significantly changed openness following the stimulation with LPS and GCM, respectively. Active genes had constitutively open promoters, but there was no direct dependence between cumulative openness of DHS regions near to a gene and its expression. LPS-regulated DHS regions were more frequent in introns, while GCM-regulated regions were more frequent away from gene bodies. GCM and LPS treatment differentially affected open chromatin regions mapped to genes in the pathways of Toll-like-receptor signaling and the Axon guidance, suggesting that the molecular machinery used by migrating microglia is similar to that of growing axons and, moreover, that modulation of these pathways is instrumental for glioma to induce a pro-invasive polarization of microglia. Our dataset of open chromatin regions active in rat microglia will constitute a useful resource for studies of the transcriptional regulation in this system. Overall design: Microglia isolated from neonate rats was maintained in cell culture and either left untreated (control group) or stimulated for 6h with either lipopolysaccharide (LPS) or C6 glioma-conditioned medium (GCM). Two independent biological replicates (microglia cultures) were prepared for each conditions, each culture obtained from 10-15 rat pups.