학술논문

Conservation and divergence of vulnerability and responses to stressors between human and mouse astrocytes
Document Type
article
Source
Nature Communications. 12(1)
Subject
Biological Sciences
Biomedical and Clinical Sciences
Genetics
Neurosciences
1.1 Normal biological development and functioning
2.1 Biological and endogenous factors
Neurological
Animals
Antigen Presentation
Astrocytes
Cells
Cultured
Gene Expression
Humans
Inactivation
Metabolic
Inflammation
Mice
Mitochondria
Nervous System Diseases
Oxidative Stress
Poly I-C
Species Specificity
Transcriptome
Tumor Necrosis Factor-alpha
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.