Single-Cell Mapping of Brain Myeloid Cell Subsets Reveals Key Transcriptomic Changes Favoring Neuroplasticity after Ischemic Stroke  

作　　者：Fangxi Liu Xi Cheng Chuansheng Zhao Xiaoqian Zhang Chang Liu Shanshan Zhong Zhouyang Liu Xinyu Lin Wei Qiu Xiuchun Zhang 

机构地区：[1]Department of Neurology.The First Affiliated Hospital of China Medical University,Shenyang 110001,China [2]Department of Neurology,The Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China [3]Stroke Center,The First Affiliated Hospital of China Medical University,Shenyang 110001,China

出　　处：《Neuroscience Bulletin》2024年第1期65-78,共14页神经科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China(82071467);the International(Regional)Cooperation and Exchange Program of the National Natural Science Foundation of China(82111330075);the National Natural Science Foundation for Youth Scholars of China(81801053);the Innovation Team Support Plan of Universities in Liaoning Province(LT2019015);the Liaoning Provincial Key Research and Development Guidance Program(2019JH8/10300002);the Liaoning Revitalization Talents Plan(XLYC1802097).

摘　　要：Interactions between brain-resident and periph-eral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia.However,con-ventional bulk sequencing makes it challenging to depict this complex immune network.Using single-cell RNA sequencing,we mapped compositional and transcriptional features of peri-infarct immune cells.Microglia were the predominant cell type in the peri-infarct region,displaying a more diverse activation pattern than the typical pro-and anti-inflammatory state,with axon tract-associated micro-glia(ATMs)being associated with neuronal regeneration.Trajectory inference suggested that infiltrated monocyte-derived macrophages(MDMs)exhibited a gradual fate trajectory transition to activated MDMs.Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis,with SOX2 and related Akt/CREB signaling as the underlying mechanisms.This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.

关 键 词：Ischemic stroke Monocyte-derived macrophage Microglia Neurogenesis Single-cell sequencing 

分 类 号：R743.3[医药卫生—神经病学与精神病学]