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Nat Commun ; 12(1): 3958, 2021 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-34172753

RESUMEN

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.


Asunto(s)
Astrocitos/fisiología , Animales , Presentación de Antígeno , Astrocitos/efectos de los fármacos , Células Cultivadas , Expresión Génica/efectos de los fármacos , Humanos , Inactivación Metabólica , Inflamación , Ratones , Mitocondrias/metabolismo , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/patología , Estrés Oxidativo , Poli I-C/farmacología , Poli I-C/uso terapéutico , Especificidad de la Especie , Transcriptoma/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacología , Factor de Necrosis Tumoral alfa/uso terapéutico
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