Propagation of neuronal micronuclei regulates microglial states

Abstract

Microglia, resident immune cells in the central nervous system, undergo morphological and functional changes in response to signals from the local environment and mature into various homeostatic states. However, niche signals underlying microglial development and maturation remain largely unknown. In this study, we show that neuronal micronuclei propagate microglia, followed by changing microglial states during the postnatal period. We discovered that neurons passing through a dense region of the developing neocortex give rise to micronuclei and release them into the extracellular space. Moreover, neuronal micronuclei were incorporated into microglia and affected morphological changes. Loss of the cGAS gene alleviates effects on micronucleus-dependent morphological changes. Notably, neuronal micronuclei-harboring microglia exhibit unique transcriptome signatures. These results demonstrate that neuronal micronuclei serve as niche signals that produce novel microglial states. Our findings provide a potential mechanism for regulating the microglial state in the early-postnatal neocortex.