This repository contains code used for: Yangning Lan, Xiaoxuan Zhang, Shaorui Liu, Chen Guo, Yuxiao Jin, Hui Li, Linyixiao Wang, Jinghong Zhao, Yilin Hao, Zhicheng Li, Zhaoyuan Liu, Florent Ginhoux, Qi Xie, Heping Xu, Jie-Min Jia, Danyang He. Fate mapping of Spp1 expression reveals age-dependent plasticity of disease-associated microglia-like cells after brain injury. Immunity. 2024, Feb 02. ISSN 1074-7613, doi: 10.1016/j.immuni.2024.01.008.
Abstract: Microglial reactivity to injury and disease is emerging as a heterogeneous, dynamic, and crucial determinant in neurological disorders. However, the plasticity and fate of disease-associated microglia (DAM) remain largely unknown. We established a lineage tracing system, leveraging the expression dynamics of secreted phosphoprotein 1（Spp1） to label and track DAM-like microglia during brain injury and recovery. Fate mapping of Spp1+ microglia during stroke in juvenile mice revealed an irreversible state of DAM-like microglia that were ultimately eliminated from the injured brain. By contrast, DAM-like microglia in the neonatal stroke models exhibited high plasticity, regaining a homeostatic signature and integrating into the microglial network after recovery. Furthermore, neonatal injury had a lasting impact on microglia, rendering them intrinsically sensitized to subsequent immune challenges. Therefore, our findings highlight the plasticity and innate immune memory of neonatal microglia, shedding light on the fate of DAM-like microglia in various neuropathological conditions.
Link to paper: https://www.cell.com/immunity/fulltext/S1074-7613(24)00032-3
Any questions about the data, please directly contact Dr. Danyang He: hedanyang@westlake.edu.cn