Single-Cell Mapping of Brain Myeloid Cell Subsets Reveals Key Transcriptomic Changes Favoring Neuroplasticity after Ischemic Stroke.
10.1007/s12264-023-01109-7
- Author:
Fangxi LIU
1
;
Xi CHENG
2
;
Chuansheng ZHAO
1
;
Xiaoqian ZHANG
1
;
Chang LIU
3
;
Shanshan ZHONG
1
;
Zhouyang LIU
1
;
Xinyu LIN
1
;
Wei QIU
4
;
Xiuchun ZHANG
5
Author Information
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.
4. Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China. qiuwei@mail.sysu.edu.cn.
5. Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China. 15204090196@163.com.
- Publication Type:Journal Article
- Keywords:
Ischemic stroke;
Microglia;
Monocyte-derived macrophage;
Neurogenesis;
Single-cell sequencing
- MeSH:
Humans;
Ischemic Stroke;
Brain/metabolism*;
Macrophages;
Brain Ischemia/metabolism*;
Microglia/metabolism*;
Gene Expression Profiling;
Anti-Inflammatory Agents;
Neuronal Plasticity/physiology*;
Infarction/metabolism*
- From:
Neuroscience Bulletin
2024;40(1):65-78
- CountryChina
- Language:English
-
Abstract:
Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional 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 microglia (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.
