Conservation and divergence of vulnerability and responses to stressors between human and mouse astrocytes

• Published in: Nature communications Vol. 12; no. 1; pp. 3958 - 20
• Main Authors: Li, Jiwen, Pan, Lin, Pembroke, William G., Rexach, Jessica E., Godoy, Marlesa I., Condro, Michael C., Alvarado, Alvaro G., Harteni, Mineli, Chen, Yen-Wei, Stiles, Linsey, Chen, Angela Y., Wanner, Ina B., Yang, Xia, Goldman, Steven A., Geschwind, Daniel H., Kornblum, Harley I., Zhang, Ye
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.06.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/51; 38/39; 38/90; 45/91; 49/40; 631/337/2019; 631/378/2596/1308; 631/378/340; Animal models; Animals; Antigen Presentation; Antigens; Astrocytes; Astrocytes - drug effects; Astrocytes - physiology; Cells, Cultured; Conservation; Detoxification; Divergence; Gene expression; Gene Expression - drug effects; Homeostasis; Humanities and Social Sciences; Humans; Hypoxia; Inactivation, Metabolic; Inflammation; Mice; Mitochondria; Mitochondria - metabolism; multidisciplinary; Nervous System Diseases - drug therapy; Nervous System Diseases - pathology; Neurodegeneration; Neurological diseases; Oxidative Stress; Poly I-C - pharmacology; Poly I-C - therapeutic use; Science; Science (multidisciplinary); Species; Species Specificity; Transcription; Transcriptome - drug effects; Tumor Necrosis Factor-alpha - pharmacology; Tumor Necrosis Factor-alpha - therapeutic use; Xenografts
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-24232-3

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. Astrocytes are important players in brain development, homeostasis, and disease. Here, the authors compare the transcriptional profiles of human and mouse astrocytes. They report species-specific susceptibility to oxidative stress and response to hypoxic and inflammatory conditions.