小胶质细胞
神经退行性变
神经炎症
生物
神经科学
硫酸软骨蛋白多糖
免疫学
病理
细胞生物学
医学
疾病
炎症
细胞外基质
蛋白多糖
作者
Ya‐Jing Liu,Yu Ding,Yanqing Yin,Hui Xiao,Gang Hu,Jiawei Zhou
标识
DOI:10.1073/pnas.2210643120
摘要
Microglia play a critical role in the pathogenic process of neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD). Upon pathological stimulation, microglia are converted from a surveillant to an overactivated phenotype. However, the molecular characters of proliferating microglia and their contributions to the pathogenesis of neurodegeneration remain unclear. Here, we identify chondroitin sulfate proteoglycan 4 (Cspg4, also known as neural/glial antigen 2)-expressing microglia as a specific subset of microglia with proliferative capability during neurodegeneration. We found that the percentage of Cspg4+ microglia was increased in mouse models of PD. The transcriptomic analysis of Cspg4+ microglia revealed that the subcluster Cspg4high microglia displayed a unique transcriptomic signature, which was characterized by the enrichment of orthologous cell cycle genes and a lower expression of genes responsible for neuroinflammation and phagocytosis. Their gene signatures were also distinct from that of known disease-associated microglia. The proliferation of quiescent Cspg4high microglia was evoked by pathological α-synuclein. Following the transplantation in the adult brain with the depletion of endogenous microglia, Cspg4high microglia grafts showed higher survival rates than their Cspg4- counterparts. Consistently, Cspg4high microglia were detected in the brain of AD patients and displayed the expansion in animal models of AD. These findings suggest that Cspg4high microglia are one of the origins of microgliosis during neurodegeneration and may open up a avenue for the treatment of neurodegenerative diseases.
科研通智能强力驱动
Strongly Powered by AbleSci AI