An Integrated Gene Expression Landscape Profiling Approach to Identify Lung Tumor Endothelial Cell Heterogeneity and Angiogenic Candidates

被引：297

作者：

Goveia, Jermaine ^{[1
,2
]}

Rohlenova, Katerina ^{[1
,2
]}

Taverna, Federico ^{[1
,2
]}

Treps, Lucas ^{[1
,2
]}

Conradi, Lena-Christin ^{[1
,2
,27
]}

Pircher, Andreas ^{[1
,2
,28
]}

Geldhof, Vincent ^{[1
,2
]}

de Rooij, Laura P. M. H. ^{[1
,2
]}

Kalucka, Joanna ^{[1
,2
,29
,30
]}

Sokol, Liliana ^{[1
,2
]}

Garcia-Caballero, Melissa ^{[1
,2
]}

Zheng, Yingfeng ^{[3
]}

Qian, Junbin ^{[2
,4
]}

Teuwen, Laure-Anne ^{[1
,2
]}

Khan, Shawez ^{[1
,2
]}

Boeckx, Bram ^{[2
,4
]}

Wauters, Els ^{[5
,6
]}

Decaluwe, Herbert ^{[5
,6
,7
]}

De Leyn, Paul ^{[5
,6
,7
]}

Vansteenkiste, Johan ^{[5
,6
]}

Weynand, Birgit ^{[8
]}

Sagaert, Xavier ^{[8
]}

Verbeken, Erik ^{[8
]}

Wolthuis, Albert ^{[9
]}

Topal, Baki ^{[9
]}

Everaert, Wouter ^{[10
,11
]}

Bohnenberger, Hanibal ^{[12
]}

Emmert, Alexander ^{[13
]}

Panovska, Dena ^{[14
]}

De Smet, Frederik ^{[14
]}

Staal, Frank J. T. ^{[15
]}

Mclaughlin, Rene J. ^{[15
]}

Impens, Francis ^{[16
,17
,18
]}

Lagani, Vincenzo ^{[19
,20
]}

Vinckier, Stefan ^{[1
,2
]}

Mazzone, Massimiliano ^{[2
,21
]}

Schoonjans, Luc ^{[1
,2
]}

Dewerchin, Mieke ^{[1
,2
]}

Eelen, Guy ^{[1
,2
]}

Karakach, Tobias K. ^{[1
,2
,31
,32
]}

Yang, Huanming ^{[22
,23
]}

Wang, Jian ^{[22
,23
]}

Bolund, Lars ^{[24
,25
]}

Lin, Lin ^{[24
,25
]}

Thienpont, Bernard ^{[26
]}

Li, Xuri ^{[3
]}

Lambrechts, Diether ^{[2
,4
]}

Luo, Yonglun ^{[22
,23
,24
,25
]}

Carmeliet, Peter ^{[1
,2
,3
]}

机构：

[1] Katholieke Univ Leuven, Lab Angiogenesis & Vasc Metab, Dept Oncol, VIB Ctr Canc Biol, B-3000 Leuven, Belgium

[2] Katholieke Univ Leuven, Leuven Canc Inst LKI, VIB Ctr Canc Biol, B-3000 Leuven, Belgium

[3] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China

[4] Katholieke Univ Leuven, VIB Ctr Canc Biol, Dept Oncol, Lab Translat Genet, B-3000 Leuven, Belgium

[5] Univ Hosp Leuven, Resp Oncol Unit Resp Med, B-3000 Leuven, Belgium

[6] Univ Hosp Leuven, Leuven Lung Canc Grp, B-3000 Leuven, Belgium

[7] Univ Hosp Leuven, Dept Thorac Surg, B-3000 Leuven, Belgium

[8] Katholieke Univ Leuven, Translat Cell & Tissue Res, Dept Imaging & Pathol, B-3000 Leuven, Belgium

[9] Katholieke Univ Leuven, Dept Abdominal Surg, Univ Hosp Leuven, B-3000 Leuven, Belgium

[10] Katholieke Univ Leuven, Dept Dev & Regenerat, Lab Expt Urol, B-3000 Leuven, Belgium

[11] Univ Hosp Leuven, Dept Urol, B-3000 Leuven, Belgium

[12] Univ Med Ctr, Inst Pathol, D-37075 Gottingen, Germany

[13] Univ Med Ctr, Dept Thorac & Cardiovasc Surg, D-37075 Gottingen, Germany

[14] Katholieke Univ Leuven, Dept Imaging & Pathol, Lab Precis Canc Med Translat Cell & Tissue Res, B-3000 Leuven, Belgium

[15] Leiden Univ, Med Ctr, Dept Immunol & Blood Transfus, NL-2300 RC Leiden, Netherlands

[16] VIB Prote Core, B-9000 Ghent, Belgium

[17] VIB Ctr Med Biotechnol, B-9000 Ghent, Belgium

[18] Univ Ghent, Dept Biomol Med, B-9000 Ghent, Belgium

[19] Ilia State Univ, Inst Chem Biol, GE-0162 Tbilisi, Georgia

[20] Gnosis Data Anal PC, GR-70013 Iraklion, Greece

[21] Katholieke Univ Leuven, Dept Oncol, Lab Tumor Inflammat & Angiogenesis, VIB Ctr Canc Biol, B-3000 Leuven, Belgium

[22] BGI Shenzhen, Shenzhen 518083, Peoples R China

[23] BGI Shenzhen, China Natl GeneBank, Shenzhen 518120, Peoples R China

[24] Aarhus Univ, Dept Biomed, DK-8000 Aarhus, Denmark

[25] BGI Qingdao, Lars Bolund Inst Regenerat Med, Qingdao 266555, Peoples R China

[26] Katholieke Univ Leuven, Dept Human Genet, Lab Funct Epigenet, B-3000 Leuven, Belgium

[27] Univ Med Ctr Gottingen, Clin Gen Visceral & Pediat Surg, D-37075 Gottingen, Germany

[28] Med Univ Innsbruck, Dept Hematol & Oncol, Internal Med 5, A-6020 Innsbruck, Austria

[29] Aarhus Inst Adv Studies, DK-8000 Aarhus, Denmark

[30] Dept Biomed, DK-8000 Aarhus, Denmark

[31] Childrens Hosp Res Inst Manitoba, Bioinformat Core Lab, Winnipeg, MB, Canada

[32] Rady Fac Hlth Sci, Dept Pediat & Child Hlth, Winnipeg, MB, Canada

来源：

CANCER CELL | 2020年 / 37卷 / 01期

基金：

奥地利科学基金会; 中国国家自然科学基金; 欧洲研究理事会;

关键词：

R-PACKAGE; VESSEL NORMALIZATION; BIOCONDUCTOR PACKAGE; INHIBITION; CANCER; IDENTIFICATION; METASTASIS; MECHANISMS; COLLAGEN; REVEAL;

D O I：

10.1016/j.ccell.2019.12.001

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Heterogeneity of lung tumor endothelial cell (TEC) phenotypes across patients, species (human/mouse), and models (in vivo/in vitro) remains poorly inventoried at the single-cell level. We single-cell RNA (scRNA)-sequenced 56,771 endothelial cells from human/mouse (peri)-tumoral lung and cultured human lung TECs, and detected 17 known and 16 previously unrecognized phenotypes, including TECs putatively regulating immune surveillance. We resolved the canonical tip TECs into a known migratory tip and a putative basement-membrane remodeling breach phenotype. Tip TEC signatures correlated with patient survival, and tip/breach TECs were most sensitive to vascular endothelial growth factor blockade. Only tip TECs were congruent across species/models and shared conserved markers. Integrated analysis of the scRNA-sequenced data with orthogonal multi-omics and meta-analysis data across different human tumors, validated by functional analysis, identified collagen modification as a candidate angiogenic pathway.

引用

页码：21 / +

页数：29

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