生物
少突胶质细胞
陶氏病
神经科学
中枢神经系统
病理
小胶质细胞
人脑
炎症
神经退行性变
疾病
免疫学
医学
髓鞘
作者
Mor Kenigsbuch,Pierre Bost,Shahar Halevi,Yuzhou Chang,Shuo Chen,Qin Ma,Renana Hajbi,Benno Schwikowski,Bernd Bodenmiller,Hongjun Fu,Michal Schwartz,Ido Amit
标识
DOI:10.1038/s41593-022-01104-7
摘要
Alzheimer's disease (AD) is a complex neurodegenerative disease, perturbing neuronal and non-neuronal cell populations. In this study, using single-cell transcriptomics, we mapped all non-immune, non-neuronal cell populations in wild-type and AD model (5xFAD) mouse brains. We identified an oligodendrocyte state that increased in association with brain pathology, which we termed disease-associated oligodendrocytes (DOLs). In a murine model of amyloidosis, DOLs appear long after plaque accumulation, and amyloid-beta (Aβ) alone was not sufficient to induce the DOL signature in vitro. DOLs could be identified in a mouse model of tauopathy and in other murine neurodegenerative and autoimmune inflammatory conditions, suggesting a common response to severe pathological conditions. Using quantitative spatial analysis of mouse and postmortem human brain tissues, we found that oligodendrocytes expressing a key DOL marker (SERPINA3N/SERPINA3 accordingly) are present in the cortex in areas of brain damage and are enriched near Aβ plaques. In postmortem human brain tissue, the expression level of this marker correlated with cognitive decline. Altogether, this study uncovers a shared signature of oligodendrocytes in central nervous system pathologies.
科研通智能强力驱动
Strongly Powered by AbleSci AI