Journal
CANCER CELL
Volume 37, Issue 1, Pages 21-+Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2019.12.001
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Funding
- Fonds Wetenschappelijk Onderzoek' (FWO)
- Fritz Thyssen Stiftung [10.16.2.017MN]
- Austrian Science Fund [J3730-B26]
- L.-A.T. by Antwerp University
- Strategisch Basisonderzoek FWO (SB-FWO)
- Kom op Tegen Kanker (Stand up to Cancer, Flemish Cancer Society)
- Methusalem funding (Flemish Government)
- Sanming Project of Medicine in Shenzhen [SZSM201612074]
- Lundbeck Foundation [R219-2016-1375]
- DFF Sapere Aude Starting grant [8048-00072A]
- Danish Research Council for Independent Research [DFF-1337-00128]
- Sapere Aude Young Research Talent Prize [DFF-1335-00763A]
- Aarhus University Strategic Grant
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center
- National Natural Science Foundation of China [81670855]
- Key Program of Guangzhou Scientific Research Plan [3030901006074]
- VIB TechWatch, Methusalem
- FWO, Foundation against Cancer [2016-078]
- Kom op tegen Kanker
- ERC [ERC-713758]
- Advanced ERC Research Grant [EU-ERC743074]
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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.
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