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

阿平添加于 2020-1-28 22:19 | 2437 次阅读 | 0 个评论

作者
Goveia J, Rohlenova K, Taverna F, Treps L, Conradi L-C, Pircher A, Geldhof V, de Rooij LPMH, Kalucka J, Sokol L, Garcia-Caballero M, Zheng Y, Qian J, Teuwen L-A, Khan S, Boeckx B, Wauters E, Decaluwe 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 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
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.
详细资料
- 关键词: angiogenesis; anti-angiogenic therapy; cancer; endothelial cells; endothelial heterogeneity; multi-omics; single-cell RNA sequencing
- 文献种类: Journal Article
- 期刊名称: Cancer Cell
- 期刊缩写: Cancer Cell
- 期卷页: 2020年第37卷第1期 21-36.e13页
- 地址: Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, Guangdong, China. Electronic address: peter.carmeliet@kuleuven.vib.be
- ISBN: 1535-6108
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内皮细胞的单细胞解析
迄今为止对肺内皮细胞最完备的描述！
想想也许对最近的2009冠状病毒研究也帮助