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

Jiwen Li, Lin Pan, William G. Pembroke, Jessica E. Rexach, Marlesa I. Godoy, Michael C. Condro, Alvaro G. Alvarado, Mineli Harteni, Yen-Wei Chen, Linsey Stiles, Angela Y. Chen, Ina B. Wanner, Xia Yang, Steven A. Goldman, Daniel H. Geschwind, Harley I. Kornblum and Ye Zhang ()
Additional contact information
Jiwen Li: David Geffen School of Medicine at the University of California
Lin Pan: David Geffen School of Medicine at the University of California
William G. Pembroke: David Geffen School of Medicine at the University of California
Jessica E. Rexach: David Geffen School of Medicine at the University of California
Marlesa I. Godoy: David Geffen School of Medicine at the University of California
Michael C. Condro: David Geffen School of Medicine at the University of California
Alvaro G. Alvarado: David Geffen School of Medicine at the University of California
Mineli Harteni: David Geffen School of Medicine at the University of California
Yen-Wei Chen: University of California
Linsey Stiles: David Geffen School of Medicine at the University of California
Angela Y. Chen: University of California
Ina B. Wanner: David Geffen School of Medicine at the University of California
Xia Yang: University of California
Steven A. Goldman: University of Rochester Medical Center
Daniel H. Geschwind: David Geffen School of Medicine at the University of California
Harley I. Kornblum: David Geffen School of Medicine at the University of California
Ye Zhang: David Geffen School of Medicine at the University of California

Nature Communications, 2021, vol. 12, issue 1, 1-20

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24232-3

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DOI: 10.1038/s41467-021-24232-3

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