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

Journal: 
Nat Commun
Publication Year: 
2021
Authors: 
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
Ye Zhang
PubMed link: 
34172753
Public Summary: 
Astrocytes, a type of brain neuron, 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. We found 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 metabolism and detoxification pathways. In addition, we find that mouse but not human astrocytes activate a molecular program for neural repair under low oxygen, whereas human but not mouse astrocytes activate the immune system under inflammatory conditions. Here, we show species-dependent properties of astrocytes, which can be informative for improving translation from mouse models to human therapies.
Scientific 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.