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. 2020 Jan 13;37(1):21-36.e13.
doi: 10.1016/j.ccell.2019.12.001.

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

Jermaine Goveia  1 , Katerina Rohlenova  1 , Federico Taverna  1 , Lucas Treps  1 , Lena-Christin Conradi  1 , Andreas Pircher  1 , Vincent Geldhof  1 , Laura P M H de Rooij  1 , Joanna Kalucka  1 , Liliana Sokol  1 , Melissa García-Caballero  1 , Yingfeng Zheng  2 , Junbin Qian  3 , Laure-Anne Teuwen  1 , Shawez Khan  1 , Bram Boeckx  3 , Els Wauters  4 , Herbert Decaluwé  5 , Paul De Leyn  5 , Johan Vansteenkiste  4 , Birgit Weynand  6 , Xavier Sagaert  6 , Erik Verbeken  6 , Albert Wolthuis  7 , Baki Topal  7 , Wouter Everaerts  8 , Hanibal Bohnenberger  9 , Alexander Emmert  10 , Dena Panovska  11 , Frederik De Smet  11 , Frank J T Staal  12 , Rene J Mclaughlin  12 , Francis Impens  13 , Vincenzo Lagani  14 , Stefan Vinckier  1 , Massimiliano Mazzone  15 , Luc Schoonjans  1 , Mieke Dewerchin  1 , Guy Eelen  1 , Tobias K Karakach  1 , Huanming Yang  16 , Jian Wang  16 , Lars Bolund  17 , Lin Lin  17 , Bernard Thienpont  18 , Xuri Li  19 , Diether Lambrechts  3 , Yonglun Luo  20 , Peter Carmeliet  21
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Free article

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

Jermaine Goveia et al. Cancer Cell. .
Free article

Erratum in

  • An Integrated Gene Expression Landscape Profiling Approach to Identify Lung Tumor Endothelial Cell Heterogeneity and Angiogenic Candidates.
    Goveia J, Rohlenova K, Taverna F, Treps L, Conradi LC, Pircher A, Geldhof V, de Rooij LPMH, Kalucka J, Sokol L, García-Caballero M, Zheng Y, Qian J, Teuwen LA, Khan S, Boeckx B, Wauters E, Decaluwé H, De Leyn P, Vansteenkiste J, Weynand B, Sagaert X, Verbeken E, Wolthuis A, Topal B, Everaerts W, Bohnenberger H, Emmert A, Panovska D, De Smet F, Staal FJT, Mclaughlin RJ, Impens F, Lagani V, Vinckier S, Mazzone M, Schoonjans L, Dewerchin M, Eelen G, Karakach TK, Yang H, Wang J, Bolund L, Lin L, Thienpont B, Li X, Lambrechts D, Luo Y, Carmeliet P. Goveia J, et al. Cancer Cell. 2020 Mar 16;37(3):421. doi: 10.1016/j.ccell.2020.03.002. Cancer Cell. 2020. PMID: 32183954 No abstract available.

Abstract

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.

Keywords: angiogenesis; anti-angiogenic therapy; cancer; endothelial cells; endothelial heterogeneity; multi-omics; single-cell RNA sequencing.

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