Abstract: Microglia are the resident immune cells of the brain, playing indispensable roles in maintaining c e rebr a l homeostas i s f rom embr yoni c development through aging (Prinz et al., 2019). Beyond their classical immune functions, microglia are now recognized as active participants in a wide range of processes, including synaptic pruning, clearance of apoptotic neurons, neurogenesis, and synaptogenesis (Borst et al., 2021). Recent fate mapping analyses have identified that microglia originate from the yolk sac and migrate into the brain primordium (Ginhoux et al., 2010). After migration, microglia colonize the embryonic brain primordium, proliferate before and after birth, and subsequently persist as long-lived selfrenewing cells within the central nervous system (Barry-Carroll et al., 2023). Once established, they undergo context-dependent state transitions characterized by distinct transcriptional profiles, thereby acquiring diverse properties and functions (Masuda et al., 2020). Recent advances in singlecell transcriptomics and in vivo imaging have further revealed remarkable heterogeneity among microglial populations. Due to this unexpected complexity, the definition of microglial heterogeneity is currently under discussion (Paolicelli et al., 2022). These specialized populations exhibit unique anatomical niches and functional repertoires, which contribute to immune surveillance, vascular integrity, and the maintenance of the blood–brain barrier. Although this diversity is thought to be shaped by a variety of signals within the brain environment, the key factors underlying such heterogeneity have remained elusive. Recently, we discovered novel mechanisms underlying the regulation of microglial properties by micronuclei (MNs) (Yano et al., 2025). In this perspective, we present our findings demonstrating that MNs act as potential mediators of neuron-to-microglia communication and consequently regulate microglial diversity.