Conservation and divergence of vulnerability and responses to stressors between human and mouse astrocytes
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Conservation and divergence of vulnerability and responses to stressors between human and mouse astrocytes. / Li, Jiwen; Pan, Lin; Godoy, Marlesa; Pembroke, William G.; Rexach, Jessica E.; Condro, Michael C.; Alvarado, Alvaro G.; Harteni, Mineli; Chen, Yen-Wei; Stiles, Linsey; Chen, Angela Y.; Wanner, Ina B.; Yang, Xia; Goldman, Steven A.; Geschwind, Daniel H.; Kornblum, Harley; Zhang, Ye.
In: Nature Communications, Vol. 12, No. 1, 3958, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Conservation and divergence of vulnerability and responses to stressors between human and mouse astrocytes
AU - Li, Jiwen
AU - Pan, Lin
AU - Godoy, Marlesa
AU - Pembroke, William G.
AU - Rexach, Jessica E.
AU - Condro, Michael C.
AU - Alvarado, Alvaro G.
AU - Harteni, Mineli
AU - Chen, Yen-Wei
AU - Stiles, Linsey
AU - Chen, Angela Y.
AU - Wanner, Ina B.
AU - Yang, Xia
AU - Goldman, Steven A.
AU - Geschwind, Daniel H.
AU - Kornblum, Harley
AU - Zhang, Ye
PY - 2021
Y1 - 2021
N2 - 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.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.
AB - 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.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.
KW - GLIAL PROGENITOR CELLS
KW - HUMAN-BRAIN
KW - OXIDATIVE STRESS
KW - RADIAL GLIA
KW - RNA-SEQ
KW - TRANSCRIPTOME
KW - MICE
KW - DISEASE
KW - MODELS
KW - PURIFICATION
U2 - 10.1038/s41467-021-24232-3
DO - 10.1038/s41467-021-24232-3
M3 - Journal article
C2 - 34172753
VL - 12
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 3958
ER -
ID: 277647227