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

Autor: Li J; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA., Pan L; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA., Pembroke WG; Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA., Rexach JE; Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA., Godoy MI; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA., Condro MC; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA., Alvarado AG; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA., Harteni M; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA., Chen YW; Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA., Stiles L; Department of Endocrinology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA., Chen AY; Department of Obstetrics and Gynecology, University of California, Los Angeles, CA, USA., Wanner IB; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.; Intellectual and Developmental Disabilities Research Center at UCLA, Los Angeles, CA, USA., Yang X; Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA.; Institute for Quantitative and Computational Biosciences at UCLA, Los Angeles, CA, USA.; Brain Research Institute at UCLA, Los Angeles, CA, USA.; Molecular Biology Institute at UCLA, Los Angeles, CA, USA., Goldman SA; Center for Translational Neuromedicine and Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA.; Center for Translational Neuromedicine, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, Denmark., Geschwind DH; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.; Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.; Department of Human Genetics, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA., Kornblum HI; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.; Intellectual and Developmental Disabilities Research Center at UCLA, Los Angeles, CA, USA.; Molecular Biology Institute at UCLA, Los Angeles, CA, USA.; Department of Pediatrics, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA., Zhang Y; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA. yezhang@ucla.edu.; Intellectual and Developmental Disabilities Research Center at UCLA, Los Angeles, CA, USA. yezhang@ucla.edu.; Brain Research Institute at UCLA, Los Angeles, CA, USA. yezhang@ucla.edu.; Molecular Biology Institute at UCLA, Los Angeles, CA, USA. yezhang@ucla.edu.; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, Los Angeles, CA, USA. yezhang@ucla.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Jun 25; Vol. 12 (1), pp. 3958. Date of Electronic Publication: 2021 Jun 25.
DOI: 10.1038/s41467-021-24232-3
Abstrakt: 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.
Databáze: MEDLINE
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