An Integrated Gene Expression Landscape Profiling Approach to Identify Lung Tumor Endothelial Cell Heterogeneity and Angiogenic Candidates
| Autor: | Albert Wolthuis, Diether Lambrechts, Xavier Sagaert, Wouter Everaerts, Junbin Qian, Yingfeng Zheng, Johan Vansteenkiste, Guy Eelen, Luc Schoonjans, Lena-Christin Conradi, Herbert Decaluwé, Alexander Emmert, Stefan Vinckier, Erik Verbeken, Paul De Leyn, Lin Lin, Shawez Khan, Birgit Weynand, Mieke Dewerchin, Lucas Treps, Liliana Sokol, Baki Topal, Bernard Thienpont, Frank J. T. Staal, Rene J. Mclaughlin, Melissa García-Caballero, Jian Wang, Federico Taverna, Peter Carmeliet, Lars Bolund, Dena Panovska, Andreas Pircher, Laure-Anne Teuwen, Yonglun Luo, Huanming Yang, Els Wauters, Joanna Kalucka, Vincent Geldhof, Francis Impens, Jermaine Goveia, Hanibal Bohnenberger, Bram Boeckx, Massimiliano Mazzone, Frederik De Smet, Vincenzo Lagani, Xuri Li, Tobias K. Karakach, Laura P.M.H. de Rooij, Katerina Rohlenova |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A 0301 basic medicine Cancer Research Lung Neoplasms Angiogenesis Angiogenesis Inhibitors BIOCONDUCTOR PACKAGE Basement Membrane anti-angiogenic therapy angiogenesis Mice chemistry.chemical_compound 0302 clinical medicine Single-cell analysis Cell Movement Carcinoma Non-Small-Cell Lung Gene expression Profiling (information science) Medicine Cluster Analysis cancer endothelial cells endothelial heterogeneity multi-omics single-cell RNA sequencing Animals Cell Line Tumor Collagen Endothelial Cells Endothelium Vascular Female Humans Phenotype Single-Cell Analysis Gene Expression Profiling Gene Expression Regulation Neoplastic Neovascularization Pathologic Non-Small-Cell Lung 0303 health sciences Tumor hemic and immune systems CANCER REVEAL Cell biology Vascular endothelial growth factor Endothelial stem cell Vascular endothelial growth factor A Oncology 030220 oncology & carcinogenesis tissues education INHIBITION Biology Cell Line MECHANISMS 03 medical and health sciences Vascular Endothelium Neovascularization 030304 developmental biology Pathologic Neoplastic IDENTIFICATION business.industry VESSEL NORMALIZATION Carcinoma R-PACKAGE Cell Biology COLLAGEN Gene expression profiling 030104 developmental biology Gene Expression Regulation chemistry METASTASIS Cancer research Lung tumor business |
| Zdroj: | Goveia, J, Rohlenova, K, Taverna, F, Treps, L, Conradi, L-C, Pircher, A, Geldhof, V, de Rooij, L P M H, Kalucka, J, Sokol, L, García-Caballero, M, Zheng, Y, Qian, J, Teuwen, L-A, Khan, S, Boeckx, B, Wauters, E, Decaluwé, H, De Leyn, P, Vansteenkiste, J, Weynand, B, Sagaert, X, Verbeken, E, Wolthuis, A, Topal, B, Everaert, W, Bohnenberger, H, Emmert, A, Panovska, D, De Smet, F, Staal, F J T, Mclaughlin, R J, Impens, F, Lagani, V, Vinckier, S, Mazzone, M, Schoonjans, L, Dewerchin, M, Eelen, G, Karakach, T K, Yang, H, Wang, J, Bolund, L, Lin, L, Thienpont, B, Li, X, Lambrechts, D, Luo, Y & Carmeliet, P 2020, ' An Integrated Gene Expression Landscape Profiling Approach to Identify Lung Tumor Endothelial Cell Heterogeneity and Angiogenic Candidates ', Cancer Cell, vol. 37, no. 1, pp. 21-36.e13 . https://doi.org/10.1016/j.ccell.2019.12.001 Cancer Cell Cancer Cell, 37(1), 21-36.e13. CELL PRESS |
| ISSN: | 1535-6108 |
| DOI: | 10.1016/j.ccell.2019.12.001 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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