Conservation and divergence of vulnerability and responses to stressors between human and mouse astrocytes.
Conservation and divergence of vulnerability and responses to stressors between human and mouse astrocytes.
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DOI：
10.1038/s41467-021-24232-3
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发表时间：
2021-06-25
影响因子：
16.6
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Li J;Pan L;Pembroke WG;Rexach JE;Godoy MI;Condro MC;Alvarado AG;Harteni M;Chen YW;Stiles L;Chen AY;Wanner IB;Yang X;Goldman SA;Geschwind DH;Kornblum HI;Zhang Y
星形胶质细胞在中风、损伤和神经变性等神经系统疾病中发挥着重要作用。大多数关于星形胶质细胞生物学的知识都是基于对小鼠模型的研究，而人类和小鼠星形胶质细胞之间的相似和不同之处还没有得到充分的描述，这给翻译研究带来了障碍。基于对急性纯化的星形胶质细胞、原代星形胶质细胞的无血清培养和异种移植的嵌合小鼠的分析，我们发现人和小鼠样本之间星形胶质细胞基因的表达广泛保守。然而，参与防御反应和新陈代谢的基因表现出物种特异性的差异。由于线粒体生理和解毒途径的不同，人星形胶质细胞比小鼠星形胶质细胞更容易受到氧化应激的影响。此外，我们发现，在低氧条件下，小鼠而不是人的星形胶质细胞激活了神经修复的分子程序，而在炎症条件下，人而不是小鼠的星形胶质细胞激活了抗原提呈途径。在这里，我们展示了星形胶质细胞的物种依赖属性，这可以为改进从小鼠模型到人类的转换提供信息。星形胶质细胞是大脑发育、动态平衡和疾病的重要参与者。在这里，作者比较了人类和小鼠星形胶质细胞的转录图谱。他们报告了物种对氧化应激的易感性以及对缺氧和炎症条件的反应。
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.
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影响因子：
25
作者：
Habib, Naomi;McCabe, Cristin;Medina, Sedi;Varshavsky, Miriam;Kitsberg, Daniel;Dvir-Szternfeld, Raz;Green, Gilad;Dionne, Danielle;Nguyen, Lan;Marshall, Jamie L.;Chen, Fei;Zhang, Feng;Kaplan, Tommy;Regev, Aviv;Schwartz, Michal
通讯作者：
Schwartz, Michal
影响因子：
5.3
作者：
Huang, YHH;Sinha, SR;Bergles, DE
通讯作者：
Bergles, DE
影响因子：
16.6
作者：
Arneson D;Zhang G;Ying Z;Zhuang Y;Byun HR;Ahn IS;Gomez-Pinilla F;Yang X
通讯作者：
Yang X
影响因子：
8.6
作者：
Bezard, Erwan;Yue, Zhenyu;Kirik, Deniz;Spillantini, Maria Grazia
通讯作者：
Spillantini, Maria Grazia
影响因子：
--
作者：
Crowley, Lisa C;Christensen, Melinda E;Waterhouse, Nigel J
通讯作者：
Waterhouse, Nigel J