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

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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.

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Acknowledgements

We would like to thank the NHC Key Laboratory of Immunodermatology (China Medical University), the Key Laboratory of Immunodermatology, and the Ministry of Education (China Medical University) for providing experimental support. This work was 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), and the Liaoning Revitalization Talents Plan (XLYC1802097).

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Author notes

  1. Fangxi Liu and Xi Cheng contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China

    Fangxi Liu, Chuansheng Zhao, Xiaoqian Zhang, Shanshan Zhong, Zhouyang Liu, Xinyu Lin & Xiuchun Zhang

  2. Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China

    Xi Cheng & Wei Qiu

  3. Stroke Center, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China

    Chuansheng Zhao & Chang Liu

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  1. Fangxi Liu
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Correspondence to Wei Qiu or Xiuchun Zhang.

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The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Liu, F., Cheng, X., Zhao, C. et al. Single-Cell Mapping of Brain Myeloid Cell Subsets Reveals Key Transcriptomic Changes Favoring Neuroplasticity after Ischemic Stroke. Neurosci. Bull. 40, 65–78 (2024). https://doi.org/10.1007/s12264-023-01109-7

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