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Project Summary

Microglia have critical roles during homeostasis of the central nervous system (CNS) and in virtually all neuroinflammatory, neuropsychiatric, neurooncological and neurodegenerative diseases. These highly diverse and specialized functions may be executed by subsets of microglia that already exist in situ or by specific states of microglia that develop from a homogenous pool of cells on demand. Recent single-cell studies have identified subsets of microglia during different disease entities in mouse and humans. However, it remains unclear how many disease-specific microglia states exist in vivo, what their transcriptional profiles, their key signalling pathways and their dynamics during CNS pathology are. It is further unclear yet, how similar microglia states in CNS disorders of mouse and man are. We will therefore comprehensively characterize and compare microglia states during several pathologies by single-cell analyses, singlemolecule fluorescence in situ hybridizations, advanced immunohisto-chemistry, computational modelling and the usage of cell-specific knock out lines. The suggested experiments will allow to define the complexity of context-specific microglia states and the molecular mechanisms by which they appear, which may provide novel inventions for therapeutic strategies.