Brain Endothelial Cells Are Exquisite Sensors of Age-Related Circulatory Cues

被引：146

作者：

Chen, Michelle B. ^{[1
]}

Yang, Andrew C. ^{[1
,2
,3
]}

Yousef, Hanadie ^{[2
]}

Lee, Davis ^{[2
]}

Chen, Winnie ^{[2
]}

Schaum, Nicholas ^{[2
,4
]}

Lehallier, Benoit ^{[2
]}

Quake, Stephen R. ^{[1
,7
]}

Wyss-Coray, Tony ^{[2
,3
,5
,6
]}

机构：

[1] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA

[2] Stanford Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA

[3] Stanford Univ, ChEM H, Stanford, CA 94305 USA

[4] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA USA

[5] VA Palo Alto Hlth Care Syst, Dept Vet Affairs, Palo Alto, CA 94304 USA

[6] Stanford Univ, Wu Tsai Neurosci Inst, Stanford, CA 94305 USA

[7] Chan Zuckerberg Biohub, Stanford, CA 94305 USA

来源：

CELL REPORTS | 2020年 / 30卷 / 13期

关键词：

OXIDATIVE STRESS; HIPPOCAMPAL NEUROGENESIS; SUPEROXIDE-DISMUTASE; ALZHEIMERS-DISEASE; COGNITIVE FUNCTION; BARRIER INTEGRITY; APOLIPOPROTEIN-E; BLOOD; DISRUPTION; MECHANISMS;

D O I：

10.1016/j.celrep.2020.03.012

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Brain endothelial cells (BECs) are key constituents of the blood-brain barrier (BBB), protecting the brain from pathogens and restricting access of circulatory factors. Yet, because circulatory proteins have prominent age-related effects on adult neurogenesis, neuroinflammation, and cognitive function in mice, we wondered whether BECs receive and potentially relay signals between the blood and brain. Using single-cell RNA sequencing of hippocampal BECs, we discover that capillary BECs-compared with arterial and venous BECs-undergo the greatest transcriptional changes in normal aging, upregulating innate immunity and oxidative stress response pathways. Short-term infusions of aged plasma into young mice recapitulate key aspects of this aging transcriptome, and remarkably, infusions of young plasma into aged mice exert rejuvenation effects on the capillary transcriptome. Together, these findings suggest that the transcriptional age of BECs is exquisitely sensitive to age-related circulatory cues and pinpoint the BBB itself as a promising therapeutic target to treat brain disease.

引用

页码：4418 / +

页数：19

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