Single-Cell Mapping of Brain Myeloid Cell Subsets Reveals Key Transcriptomic Changes Favoring Neuroplasticity after Ischemic Stroke
Fangxi Liu1 · Xi Cheng2 · Chuansheng Zhao1,3 · Xiaoqian Zhang1 · Chang Liu3 · Shanshan Zhong1 · Zhouyang Liu1 · Xinyu Lin1 · Wei Qiu2 · Xiuchun Zhang11 Department of Neurology, The First Afliated Hospital of China Medical University, Shenyang 110001, China
2 Department of Neurology, The Third Afliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
3 Stroke Center, The First Afliated Hospital of China Medical University, Shenyang 110001, China
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.
Keywords
Ischemic stroke; Monocyte-derived macrophage; Microglia; Neurogenesis; Single-cell sequencing
