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单细胞 RNA 测序分析揭示了缺血性脑卒中急性期星形胶质细胞代谢途径的异质性和动态变化。

Single-Cell RNA-Sequencing Analyses Revealed Heterogeneity and Dynamic Changes of Metabolic Pathways in Astrocytes at the Acute Phase of Ischemic Stroke.

机构信息

Neurovascular Center, Changhai Hospital, Naval Medical University, Shanghai, China.

Department of Orthopaedic Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China.

出版信息

Oxid Med Cell Longev. 2022 Apr 30;2022:1817721. doi: 10.1155/2022/1817721. eCollection 2022.

DOI:10.1155/2022/1817721
PMID:35535357
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9078813/
Abstract

Astrocyte plays important roles in the pathogenesis of ischemic stroke and reperfusion injury. They intensively participate in the energy metabolism of the brain, while their heterogeneity and function after ischemic stroke remain controversial. By employing single-cell sequencing of mice cortex at 12 h after transient middle cerebral artery occlusion (tMCAO) and comparing with the similar published datasets of 24h after tMCAO, we uncover the cellular phenotypes and dynamic change of astrocytes at the acute phase of ischemic stroke. In this study, we separately identified 3 major subtypes of astrocytes at the 12 h-tMCAO-system and 24 h-tMCAO-system, indicated the significant differences in the expression of genes and metabolic pathways in the astrocytes between the two time nodes after ischemic stroke, and detected the major change in the energy metabolism. These results provided a comprehensive understanding of the characteristic changes of astrocytes after ischemic stroke and explored the potential astrocytic targets for neuroprotection.

摘要

星形胶质细胞在缺血性中风和再灌注损伤的发病机制中起着重要作用。它们积极参与大脑的能量代谢,但其在缺血性中风后的异质性和功能仍存在争议。通过对短暂性大脑中动脉闭塞(tMCAO)后 12 小时的小鼠皮层进行单细胞测序,并与 tMCAO 后 24 小时的类似已发表数据集进行比较,我们揭示了缺血性中风急性期星形胶质细胞的细胞表型和动态变化。在这项研究中,我们分别在 12 小时-tMCAO 系统和 24 小时-tMCAO 系统中鉴定出 3 种主要的星形胶质细胞亚型,表明缺血性中风后两个时间节点星形胶质细胞中基因和代谢途径的表达存在显著差异,并检测到能量代谢的主要变化。这些结果提供了对缺血性中风后星形胶质细胞特征变化的全面了解,并探索了潜在的神经保护星形胶质细胞靶点。

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