小胶质细胞
吞噬作用
基因
神经炎症
发病机制
炎症
神经科学
神经退行性变
医学
细胞生物学
先天免疫系统
生物
免疫学
遗传学
疾病
免疫系统
病理
作者
Julia Marschallinger,Tal Iram,Macy E. Zardeneta,Song Eun Lee,Benoit Lehallier,Michael S. Haney,John V. Pluvinage,Vidhu Mathur,Oliver Hahn,David W. Morgens,Justin S. Kim,Julia Tevini,Thomas K. Felder,Heimo Wolinski,Carolyn R. Bertozzi,Michael C. Bassik,Ludwig Aigner,Tony Wyss‐Coray
摘要
Abstract Microglia become progressively activated and seemingly dysfunctional with age, and genetic studies have linked these cells to the pathogenesis of a growing number of neurodegenerative diseases. Here we report a striking buildup of lipid droplets in microglia with aging in mouse and human brains. These cells, which we call lipid droplet-accumulating microglia (LAM), are defective in phagocytosis, produce high levels of reactive oxygen species, and secrete pro-inflammatory cytokines. RNA sequencing analysis of LAM revealed a transcriptional profile driven by innate inflammation distinct from previously reported microglial states. An unbiased CRISPR-Cas9 screen identified genetic modifiers of lipid droplet formation; surprisingly, variants of several of these genes, including progranulin, are causes of autosomal dominant forms of human neurodegenerative diseases. We thus propose that LAM contribute to age-related and genetic forms of neurodegeneration.
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