Mouse microglial cell RNA sequencing for "Local cues establish and maintain region-specific phenotypes of basal ganglia microglia" project

Microglia play critical roles in CNS injury responses, tissue homeostasis, and can alsomodulate neuronal function and synaptic connectivity. In contrast to astrocytes andoligodendrocytes, which arise from multiple progenitor pools, microglia arise from yolk sacprogenitors and are widely considered to be equivalent throughout the CNS. However, littleis known about the features of deep brain microglia, such as those residing within the basalganglia (BG). Here, we show that microglial anatomical features, lysosome content, andmembrane properties differ significantly across BG nuclei. In addition, transcriptomesequencing revealed prominent differences in gene expression between midbrain andcortical microglia. Region-specific phenotypes of BG microglia emerged during the secondpostnatal week and were re-established following genetic or pharmacological microglialablation and repopulation in the adult, indicating that local cues play an ongoing role inshaping microglial diversity. Together, these observations demonstrate that microglia inthe healthy brain exist along a spectrum of distinct functional states and these data providea critical foundation for defining microglial contributions to BG circuit function.