SSBD:database

Sarasa Yano, Natsu Asami, Yusuke Kishi, Ikuko Takeda, Hikari Kubotani, Yuki Hattori, Ayako Kitazawa, Kanehiro Hayashi, Ken-Ichiro Kubo, Mai Saeki, Chihiro Maeda, Chihiro Hiraki, Rin-Ichiro Teruya, Takumi Taketomi, Kaito Akiyama, Tomomi Okajima-Takahashi, Ban Sato, Hiroaki Wake, Yukiko Gotoh, Kazunori Nakajima, Takeshi Ichinohe, Takeshi Nagata, Tomoki Chiba, Fuminori Tsuruta (2025) Propagation of neuronal micronuclei regulates microglial characteristics., Nature neuroscience

Published in 2025 Jan 17 (Electronic publication in Jan. 17, 2025, midnight )

• doi: 10.1038/s41593-024-01863-5
• pmid: 39825140
  

(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 differentiation and maturation remain unknown. Here, we 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.