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

Author

Listed:
  • 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
    Intellectual and Developmental Disabilities Research Center at UCLA)

  • Xia Yang

    (University of California
    Institute for Quantitative and Computational Biosciences at UCLA
    Brain Research Institute at UCLA
    Molecular Biology Institute at UCLA)

  • Steven A. Goldman

    (University of Rochester Medical Center
    University of Copenhagen Faculty of Health and Medical Sciences)

  • Daniel H. Geschwind

    (David Geffen School of Medicine at the University of California
    David Geffen School of Medicine at the University of California
    David Geffen School of Medicine at the University of California)

  • Harley I. Kornblum

    (David Geffen School of Medicine at the University of California
    Intellectual and Developmental Disabilities Research Center at UCLA
    Molecular Biology Institute at UCLA
    David Geffen School of Medicine at the University of California)

  • Ye Zhang

    (David Geffen School of Medicine at the University of California
    Intellectual and Developmental Disabilities Research Center at UCLA
    Brain Research Institute at UCLA
    Molecular Biology Institute at UCLA)

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.

Suggested Citation

  • 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. Wanne, 2021. "Conservation and divergence of vulnerability and responses to stressors between human and mouse astrocytes," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24232-3
    DOI: 10.1038/s41467-021-24232-3
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    Cited by:

    1. Fang Guo & Jun Fan & Jin-Ming Liu & Peng-Li Kong & Jing Ren & Jia-Wen Mo & Cheng-Lin Lu & Qiu-Ling Zhong & Liang-Yu Chen & Hao-Tian Jiang & Canyuan Zhang & You-Lu Wen & Ting-Ting Gu & Shu-Ji Li & Ying, 2024. "Astrocytic ALKBH5 in stress response contributes to depressive-like behaviors in mice," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Amy J. Gleichman & Riki Kawaguchi & Michael V. Sofroniew & S. Thomas Carmichael, 2023. "A toolbox of astrocyte-specific, serotype-independent adeno-associated viral vectors using microRNA targeting sequences," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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