Conservation and divergence of vulnerability and responses to stressors between human and mouse astrocytes
| Autor: | Marlesa Godoy, Xia Yang, Jiwen Li, William G Pembroke, Lin Pan, Michael C. Condro, Harley I. Kornblum, Jessica E. Rexach, Steven A. Goldman, Daniel H. Geschwind, Linsey Stiles, Yen-Wei Chen, Angela Y. Chen, Ye Zhang, Mineli Harteni, Ina B. Wanner, Alvaro G. Alvarado |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
General Physics and Astronomy HUMAN-BRAIN Gene Expression Mitochondrion medicine.disease_cause DISEASE Inactivation Mice 0302 clinical medicine Gene expression 2.1 Biological and endogenous factors RNA-SEQ Aetiology Cells Cultured Antigen Presentation Multidisciplinary Cultured Neurodegeneration Translation (biology) Antigen Presentation Pathway Cell biology Mitochondria medicine.anatomical_structure Inactivation Metabolic Neurological medicine.symptom Astrocyte Biotechnology RADIAL GLIA Science 1.1 Normal biological development and functioning Cells MODELS Biology Molecular neuroscience Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Species Specificity Underpinning research Genetics medicine Animals Humans Transcriptomics Gene Inflammation PURIFICATION Tumor Necrosis Factor-alpha Neurosciences General Chemistry Hypoxia (medical) medicine.disease Brain Disorders GLIAL PROGENITOR CELLS Oxidative Stress 030104 developmental biology Poly I-C Astrocytes Metabolic Nervous System Diseases Transcriptome 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Nature communications, vol 12, iss 1 Li, J, Pan, L, Godoy, M, Pembroke, W G, Rexach, J E, Condro, M C, Alvarado, A G, Harteni, M, Chen, Y-W, Stiles, L, Chen, A Y, Wanner, I B, Yang, X, Goldman, S A, Geschwind, D H, Kornblum, H & Zhang, Y 2021, ' Conservation and divergence of vulnerability and responses to stressors between human and mouse astrocytes ', Nature Communications, vol. 12, no. 1, 3958 . https://doi.org/10.1038/s41467-021-24232-3 Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-20 (2021) |
| DOI: | 10.1038/s41467-021-24232-3 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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