Microglia in developing retina transition through a disease-like functional state that does not require CSF1R signaling for survival

Microglia have important remodeling functions in development and disease. There is evidence for molecular diversity of microglia suggesting they may exist in distinct functional states to differentially impact CNS health and function. To better understand this in development, we profiled microglia of a discrete developing CNS region, the murine retina. We find that retinal microglia transition through unique transcriptional states and identify a population with peak density postnatally that resemble adult disease-associated microglia (DAM) and CD11c+ microglia of developing white matter, we term DAM-like. Developmental cell death is a major driver of the DAM-like phenotype, and TREM2 signaling is required for select DAM gene expression. Notably, DAM-like cells that highly express CD11c are not dependent on CSF1R signaling for survival, and TREM2 signaling is required for CSF1R independence in a subset of microglia. Thus, microglial phenotype in development is influenced by local developmental events and may share features with microglia in disease. Overall design: mRNA profiles of whole retina and sorted retinal microglia from embryonic day (e)16.5, postnatal day (P)7 and adult (P60) mice were generated by deep sequencing.

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Anderson SR, Roberts JM, Zhang J, Steele MR, Romero CO, Bosco A, Vetter ML