학술논문

Conservation and divergence of vulnerability and responses to stressors between human and mouse astrocytes.
Document Type
article
Source
Nature communications. 12(1)
Subject
Astrocytes
Cells
Cultured
Mitochondria
Animals
Humans
Mice
Nervous System Diseases
Inflammation
Tumor Necrosis Factor-alpha
Poly I-C
Species Specificity
Antigen Presentation
Gene Expression
Oxidative Stress
Transcriptome
Inactivation
Metabolic
Language
Abstract
Astrocytes play important roles in neurological disorders such as stroke, injury, and neurodegeneration. Most knowledge on astrocyte biology is based on studies of mouse models and the similarities and differences between human and mouse astrocytes are insufficiently characterized, presenting a barrier in translational research. Based on analyses of acutely purified astrocytes, serum-free cultures of primary astrocytes, and xenografted chimeric mice, we find extensive conservation in astrocytic gene expression between human and mouse samples. However, the genes involved in defense response and metabolism show species-specific differences. Human astrocytes exhibit greater susceptibility to oxidative stress than mouse astrocytes, due to differences in mitochondrial physiology and detoxification pathways. In addition, we find that mouse but not human astrocytes activate a molecular program for neural repair under hypoxia, whereas human but not mouse astrocytes activate the antigen presentation pathway under inflammatory conditions. Here, we show species-dependent properties of astrocytes, which can be informative for improving translation from mouse models to humans.