Integrative analysis of the human brain mural cell transcriptome

被引:19
|
作者
Gastfriend, Benjamin D. [1 ]
Foreman, Koji L. [1 ]
Katt, Moriah E. [1 ]
Palecek, Sean P. [1 ]
Shusta, Eric, V [1 ,2 ]
机构
[1] Univ Wisconsin, Dept Chem & Biol Engn, 1415 Engn Dr, Madison, WI 53706 USA
[2] Univ Wisconsin, Dept Neurol Surg, 1415 Engn Dr, Madison, WI 53706 USA
来源
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM | 2021年 / 41卷 / 11期
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
Brain mural cells; pericytes; vascular smooth muscle cells; single cell RNA-sequencing; neurovascular unit; SMOOTH-MUSCLE-CELLS; FIBROBLASTS FORM; MESSENGER-RNA; FIBROTIC SCAR; BLOOD-FLOW; PERICYTES; MOUSE; EXPRESSION; INTEGRITY; SEQ;
D O I
10.1177/0271678X211013700
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Brain mural cells, including pericytes and vascular smooth muscle cells, are important for vascular development, blood-brain barrier function, and neurovascular coupling, but the molecular characteristics of human brain mural cells are incompletely characterized. Single cell RNA-sequencing (scRNA-seq) is increasingly being applied to assess cellular diversity in the human brain, but the scarcity of mural cells in whole brain samples has limited their molecular profiling. Here, we leverage the combined power of multiple independent human brain scRNA-seq datasets to build a transcriptomic database of human brain mural cells. We use this combined dataset to determine human-mouse species differences in mural cell transcriptomes, culture-induced dedifferentiation of human brain pericytes, and human mural cell organotypicity, with several key findings validated by RNA fluorescence in situ hybridization. Together, this work improves knowledge regarding the molecular constituents of human brain mural cells, serves as a resource for hypothesis generation in understanding brain mural cell function, and will facilitate comparative evaluation of animal and in vitro models.
引用
收藏
页码:3052 / 3068
页数:17
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