Decoding the Transcriptional Response to Ischemic Stroke in Young and Aged Mouse Brain
Decoding the Transcriptional Response to Ischemic Stroke in Young and Aged Mouse Brain
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DOI：
10.1016/j.celrep.2020.107777
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发表时间：
2020-06-16
期刊：
影响因子：
8.8
通讯作者：
Valihrach, Lukas
中科院分区：
文献类型：
--
作者：
Androvic, Peter;Kirdajova, Denisa;Valihrach, Lukas
缺血性中风是一种公认的衰老性疾病，但目前尚不清楚这种年龄依赖性易感性是如何发生的，其潜在机制是什么。为了解决这些问题，我们在3个月和18个月大的小鼠中对衰老、缺血性中风及其相互作用进行了全面的RNA-seq分析。我们评估了不同损伤状态和年龄的差异基因表达，估计细胞类型比例的变化，根据文献中的一系列转录特征分析结果，并进行无监督的共表达分析，确定对损伤有不同反应的基因模块。我们发现老年小鼠中风后轴突和突触维持遗传程序下调，I型干扰素（IFN-I）信号的激活增加。总之，这些结果描绘了缺血性中风作为一种复杂的年龄相关疾病的图景，并在细胞和分子水平上为衰老和中风的相互作用提供了见解。
Ischemic stroke is a well-recognized disease of aging, yet it is unclear how the age-dependent vulnerability occurs and what are the underlying mechanisms. To address these issues, we perform a comprehensive RNA-seq analysis of aging, ischemic stroke, and their interaction in 3- and 18-month-old mice. We assess differential gene expression across injury status and age, estimate cell type proportion changes, assay the results against a range of transcriptional signatures from the literature, and perform unsupervised co-expression analysis, identifying modules of genes with varying response to injury. We uncover downregulation of axonal and synaptic maintenance genetic program, and increased activation of type I interferon (IFN-I) signaling following stroke in aged mice. Together, these results paint a picture of ischemic stroke as a complex age-related disease and provide insights into interaction of aging and stroke on cellular and molecular level.