Final Report Summary - DMR-CODE (Decoding the Mammalian transcriptional Regulatory code in development and stimulatory responses)
The immune system safeguards the host organism against pathogens, neurodegeneration, metabolic disease and cancer but, concurrently, must also avoid attacking its own healthy cells and tissues. To achieve this balance, the activity of immune cells is controlled by a complex array of positive and negative regulatory mechanisms. Consistently, immune cell subsets display high diversity that is determined by interactions with the surrounding tissue. These highly complex niches involve communication between heterogeneous groups of cells and genomic elements. Our research developed new single-cell genomic technologies to analyze complex immune cell populations and regulatory circuits in multiple niches consisting of stem cells and various differentiated immune cells, as well as the cross-talk among them. These new technologies enabled us to greatly facilitate reconstruction of spatial genomic blueprints of the immune system in different physiological and pathological models. Our research produced methodological and conceptual breakthroughs in various immune processes by characterizing the diversity and dynamics of the different cell types within the immune system, (2) identified pathways, genes, markers and mechanisms of regulation, and (3) carefully tested various immune-related responses in both health and disease which are being translated into innovate new targets for immunotherapy in autoimmune diseases, neurodegeneration and cancer.