Bioinformatics analysis identified apolipoprotein E as a hub gene regulating neuroinflammation in macrophages and microglia following spinal cord injury.

Autor: Yao XQ; Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China., Chen JY; Department of Comprehensive Medical Treatment Ward, Nanfang Hospital, Southern Medical University, Guangzhou, China., Yu ZH; Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China., Huang ZC; Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China., Hamel R; Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom., Zeng YQ; Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China., Huang ZP; Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China., Tu KW; Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China., Liu JH; Division of Spine Surgery, Department of Orthopaedics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China., Lu YM; Center of Electron Microscopy, Central Laboratory, Southern Medical University, Guangzhou, China., Zhou ZT; Center of Electron Microscopy, Central Laboratory, Southern Medical University, Guangzhou, China., Pluchino S; Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom., Zhu QA; Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China., Chen JT; Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Jazyk: angličtina
Zdroj: Frontiers in immunology [Front Immunol] 2022 Aug 24; Vol. 13, pp. 964138. Date of Electronic Publication: 2022 Aug 24 (Print Publication: 2022).
DOI: 10.3389/fimmu.2022.964138
Abstrakt: Macrophages and microglia play important roles in chronic neuroinflammation following spinal cord injury (SCI). Although macrophages and microglia have similar functions, their phagocytic and homeostatic abilities differ. It is difficult to distinguish between these two populations in vivo , but single-cell analysis can improve our understanding of their identity and heterogeneity. We conducted bioinformatics analysis of the single-cell RNA sequencing dataset GSE159638, identifying apolipoprotein E (APOE) as a hub gene in both macrophages and microglia in the subacute and chronic phases of SCI. We then validated these transcriptomic changes in a mouse model of cervical spinal cord hemi-contusion and observed myelin uptake, lipid droplets, and lysosome accumulation in macrophages and microglia following SCI. Finally, we observed that knocking out APOE aggravated neurological dysfunction, increased neuroinflammation, and exacerbated the loss of white matter. Targeting APOE and the related cholesterol efflux represents a promising strategy for reducing neuroinflammation and promoting recovery following SCI.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Yao, Chen, Yu, Huang, Hamel, Zeng, Huang, Tu, Liu, Lu, Zhou, Pluchino, Zhu and Chen.)
Databáze: MEDLINE