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

Published version
Peer-reviewed

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Authors

Yao, Xin-Qiang 
Chen, Jia-Ying 
Yu, Zi-Han 
Huang, Zu-Cheng 
Hamel, Regan 

Abstract

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.

Description

Keywords

apolipoprotein E, bioinformatics analysis, macrophages, microglia, neuroinflammation, spinal cord injury, Animals, Apolipoproteins E, Computational Biology, Macrophages, Mice, Microglia, Neuroinflammatory Diseases, Spinal Cord Injuries

Journal Title

Front Immunol

Conference Name

Journal ISSN

1664-3224
1664-3224

Volume Title

Publisher

Frontiers Media SA