A molecular atlas of cell types and zonation in the brain vasculature

被引:1255
作者
Vanlandewijck, Michael [1 ,3 ]
He, Liqun [2 ]
Mae, Maarj A. Andaloussi [3 ]
Andrae, Johanna [3 ]
Ando, Koji [3 ]
Del Gaudio, Francesca [4 ]
Nahar, Khayrun [3 ]
Lebouvier, Thibaud [3 ,5 ]
Lavina, Barbara [3 ]
Gouveia, Leonor [3 ]
Sun, Ying [6 ]
Raschperger, Elisabeth [1 ]
Rasanen, Markus [7 ,8 ]
Zarb, Yvette [9 ]
Mochizuki, Naoki [10 ,11 ]
Keller, Annika [9 ]
Lendahl, Urban [4 ]
Betsholtz, Christer [1 ,3 ]
机构
[1] Karolinska Inst, AstraZeneca Integrated Cardio Metab Ctr KI AZ ICM, Blickagangen 6, SE-14157 Huddinge, Sweden
[2] Tianjin Med Univ, Key Lab Postneuroinjury Neurorepair & Regenerat C, Dept Neurosurg,Gen Hosp, Tianjin Neurol Inst,Minist Educ & Tianjin City, Tianjin 300052, Peoples R China
[3] Uppsala Univ, Rudbeck Lab, Dept Immunol Genet & Pathol, Dag Hammarskjolds Vag 20, SE-75185 Uppsala, Sweden
[4] Karolinska Inst, Dept Cell & Mol Biol, Von Eulers Vag 3, SE-17177 Stockholm, Sweden
[5] Univ Lille, CHU,Memory Ctr, Distalz, Inserm,U1171, F-59000 Lille, France
[6] Zhongyuan Union Genet Technol Co Ltd, Dept Bioinformat, Tianjin Airport Econ Area, 45 9th East Rd, Tianjin 300304, Peoples R China
[7] Univ Helsinki, Wihuri Res Inst, Haartmaninkatu 8,POB 63, FI-00014 Helsinki, Finland
[8] Univ Helsinki, Translat Canc Biol Program, Biomedicum Helsinki, Haartmaninkatu 8,POB 63, FI-00014 Helsinki, Finland
[9] Zurich Univ, Univ Zurich Hosp, Div Neurosurg, CH-8091 Zurich, Switzerland
[10] Natl Cerebral & Cardiovasc Ctr, Dept Cell Biol, Res Inst, Suita, Osaka, Japan
[11] Natl Cerebral & Cardiovasc Ctr, AMED CREST, Suita, Osaka, Japan
基金
瑞典研究理事会; 瑞士国家科学基金会; 欧洲研究理事会;
关键词
MESENCHYMAL STEM-CELLS; BMX TYROSINE KINASE; ENDOTHELIAL-CELLS; GENE-EXPRESSION; BARRIER TRANSPORT; BLOOD-FLOW; RNA-SEQ; PERICYTES; ORIGIN; EFFLUX;
D O I
10.1038/nature25739
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cerebrovascular disease is the third most common cause of death in developed countries, but our understanding of the cells that compose the cerebral vasculature is limited. Here, using vascular single-cell transcriptomics, we provide molecular definitions for the principal types of blood vascular and vessel-associated cells in the adult mouse brain. We uncover the transcriptional basis of the gradual phenotypic change (zonation) along the arteriovenous axis and reveal unexpected cell type differences: a seamless continuum for endothelial cells versus a punctuated continuum for mural cells. We also provide insight into pericyte organotypicity and define a population of perivascular fibroblast-like cells that are present on all vessel types except capillaries. Our work illustrates the power of single-cell transcriptomics to decode the higher organizational principles of a tissue and may provide the initial chapter in a molecular encyclopaedia of the mammalian vasculature.
引用
收藏
页码:475 / +
页数:34
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