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Single-cell RNA sequencing identifies senescent cerebromicrovascular endothelial cells in the aged mouse brain.
GeroScience ( IF 5.3 ) Pub Date : 2020-03-31 , DOI: 10.1007/s11357-020-00177-1
Tamas Kiss 1, 2 , Ádám Nyúl-Tóth 1, 3 , Priya Balasubramanian 1 , Stefano Tarantini 1, 4, 5 , Chetan Ahire 1 , Jordan DelFavero 1 , Andriy Yabluchanskiy 1, 5 , Tamas Csipo 1, 4, 6 , Eszter Farkas 2 , Graham Wiley 7 , Lori Garman 7 , Anna Csiszar 1, 2, 8 , Zoltan Ungvari 1, 2, 4, 5, 8
Affiliation  

Age-related phenotypic changes of cerebromicrovascular endothelial cells lead to dysregulation of cerebral blood flow and blood-brain barrier disruption, promoting the pathogenesis of vascular cognitive impairment (VCI). In recent years, endothelial cell senescence has emerged as a potential mechanism contributing to microvascular pathologies opening the avenue to the therapeutic exploitation of senolytic drugs in preclinical studies. However, difficulties with the detection of senescent endothelial cells in wild type mouse models of aging hinder the assessment of the efficiency of senolytic treatments. To detect senescent endothelial cells in the aging mouse brain, we analyzed 4233 cells in fractions enriched for cerebromicrovascular endothelial cells and other cells associated with the neurovascular unit obtained from young (3-month-old) and aged (28-month-old) C57BL/6 mice. We define 13 transcriptomic cell types by deep, single-cell RNA sequencing. We match transcriptomic signatures of cellular senescence to endothelial cells identified on the basis of their gene expression profile. Our study demonstrates that with advanced aging, there is an increased ratio of senescent endothelial cells (~ 10%) in the mouse cerebral microcirculation. We propose that our single-cell RNA sequencing–based method can be adapted to study the effect of aging on senescence in various brain cell types as well as to evaluate the efficiency of various senolytic regimens in multiple tissues.

中文翻译:

单细胞 RNA 测序鉴定了老年小鼠大脑中衰老的脑微血管内皮细胞。

脑微血管内皮细胞的年龄相关表型变化导致脑血流失调和血脑屏障破坏,促进血管性认知障碍(VCI)的发病机制。近年来,内皮细胞衰老已成为导致微血管病变的潜在机制,为临床前研究中对衰老药物的治疗性开发开辟了道路。然而,在衰老的野生型小鼠模型中检测衰老内皮细胞的困难阻碍了对衰老治疗效率的评估。为了检测衰老小鼠大脑中衰老的内皮细胞,我们分析了富含脑微血管内皮细胞和其他与从年轻(3 个月大)和年老(28 个月大)C57BL/6 小鼠获得的神经血管单元相关的细胞的 4233 个细胞。我们通过深度单细胞 RNA 测序定义了 13 种转录组细胞类型。我们将细胞衰老的转录组学特征与根据基因表达谱鉴定的内皮细胞相匹配。我们的研究表明,随着衰老的加剧,小鼠大脑微循环中衰老内皮细胞的比例增加 (~ 10%)。我们建议我们基于单细胞 RNA 测序的方法可以适用于研究衰老对各种脑细胞类型衰老的影响,以及评估多种组织中各种衰老方案的效率。我们通过深度单细胞 RNA 测序定义了 13 种转录组细胞类型。我们将细胞衰老的转录组学特征与根据基因表达谱鉴定的内皮细胞相匹配。我们的研究表明,随着衰老的加剧,小鼠大脑微循环中衰老内皮细胞的比例增加 (~ 10%)。我们建议我们基于单细胞 RNA 测序的方法可以适用于研究衰老对各种脑细胞类型衰老的影响,以及评估多种组织中各种衰老方案的效率。我们通过深度单细胞 RNA 测序定义了 13 种转录组细胞类型。我们将细胞衰老的转录组学特征与根据基因表达谱鉴定的内皮细胞相匹配。我们的研究表明,随着衰老的加剧,小鼠大脑微循环中衰老内皮细胞的比例增加 (~ 10%)。我们建议我们基于单细胞 RNA 测序的方法可以适用于研究衰老对各种脑细胞类型衰老的影响,以及评估多种组织中各种衰老方案的效率。小鼠大脑微循环中衰老内皮细胞的比例增加 (~ 10%)。我们建议我们基于单细胞 RNA 测序的方法可以适用于研究衰老对各种脑细胞类型衰老的影响,以及评估多种组织中各种衰老方案的效率。小鼠大脑微循环中衰老内皮细胞的比例增加 (~ 10%)。我们建议我们基于单细胞 RNA 测序的方法可以适用于研究衰老对各种脑细胞类型衰老的影响,以及评估多种组织中各种衰老方案的效率。
更新日期:2020-03-31
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