Description
Microglia-resident immune cells in the central nervous system-undergomorphological and functional changes in response to signals from thelocal environment and mature into various homeostatic states. However, niche signals underlying microglial differentiation and maturationremain unknown. Here, the authors show that neuronal micronuclei (MN) transfer to microglia, which is followed by changing microglial characteristics during the postnatal period. Neurons passing through a dense region of the developing neocortex give rise to MN and release them into the extracellular space, before being incorporated into microglia and inducing morphological changes. Two-photon imaging analyses have revealed that microglia incorporating MN tend to slowly retract their processes. Loss of the cGAS gene alleviates effects on micronucleus-dependent morphological changes. Neuronal MN-harboring microglia also exhibit unique transcriptome signatures. These results demonstrate that neuronal MN serve as niche signals that transform microglia, and provide a potential mechanism for regulation of microglial characteristics in the early postnatal neocortex.
Funding Information
This study was supported by the Cooperative Study Program (24NIPS330) of National Institute for Physiological Sciences. This work was supported by Grant-in-Aid from the Ministry of Education, Science, Sports and Culture of Japan JSPS KAKENHI [16KK0158 (F.T.), 20K05951 (F.T.), 23H04214 (Y.K.), 24K02020 (Y.K.), JP20H05688 (K.N.), JP22K19365 (K.N.), JSPS Research Fellowship for Young Scientists (19J20619 (S.Y.), 23KJ0285 (T.T.)], AMED PRIME [24028934 (F.T.)], Kao foundation for health science (F.T.), Gout and uric acid foundation (F.T.), Asahi Glass Foundation (Y.K.), SECOM Science and Technology Foundation (Y.K.) and was partly supported by Center for Quantum and Information Life Sciences (F.T.).