Exploring the role of endogenous C1q in murine microglia 4470

Abstract Description C1q is well known for activation of the classical complement pathway, and clearance of pathogens. C1q is also an opsonin, binding damaged-self targets such as apoptotic cells, and enhancing phagocytosis. C1q bound to targets decreases inflammation and increases survival in macrophages which may be important in reducing autoimmune responses. Previously we have shown that endogenous C1q modulates lipid and mitochondrial metabolic pathways in macrophages. Here we investigate if similar pathways are modulated by endogenous C1q in microglia. The effects of endogenous C1q were investigated using primary adult murine microglia from wild-type and C1q-deficient (C1q-/-) mice. Unbiased transcriptomic and lipidomic analyses were performed. RNA was isolated from wild-type and C1q-deficient microglia and sequencing libraries prepared. RNA-sequencing data showed that the presence of C1q modulated expression over 600 genes involved in a variety of cellular processes including VSIG4, Wnt signaling, and adhesion. Experiments will be performed to examine functional changes to these pathways. Lipidome changes will be evaluated to determine if C1q reduces expression of 25-hydroxycholesterol, similar to reductions observed in macrophages. Overall, the preliminary data generated shows that endogenous C1q is modulating expression of genes involved in numerous cellular processes in microglia. C1q influence on microglial cellular processes may be important in brain-related inflammatory diseases. Funding Sources This research was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Numbers 1R16GM149507 and T32GM138075. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Topic Categories Neuroimmunology (NEUR)