Project Summary

Microglia proliferation and expansion are key determinants that enable functional heterogeneity of microglia in distinct brain regions. Local microglia diversity is essentially required to ensure their defined regulatory functions for neural cells in specialized brain regions during development, health and disease. However, the mechanisms that underlie their spatial heterogeneity are poorly understood. To better understand how and when microglia multiplicity in the CNS occurs we will analyze the transcriptional landscape of these cells at conditions of high cell expansion, namely during ontogeny and in diseases. We will map these genomic circuits during microglia expansion utilizing high-throughput chromatin immunoprecipitation for genome-wide mapping of in vivo protein-DNA interactions with special focus on proliferation-linked transcription factors. These transcriptional profiles will finally be compared with spatial and temporal aspects of microglia spreading in living animals during development and in disease models by using 2-Photon in vivo imaging. We hypothesize that microglia expansion is a highly heterogeneous state in which microglia activities are altered to respond to specific environmental cues. Defining the transcriptome databases for potential subtypes of microglia will be highly useful for providing new insights into microglia function.