[PDF][PDF] An integrated gene expression landscape profiling approach to identify lung tumor endothelial cell heterogeneity and angiogenic candidates

J Goveia, K Rohlenova, F Taverna, L Treps… - Cancer cell, 2020 - cell.com
J Goveia, K Rohlenova, F Taverna, L Treps, LC Conradi, A Pircher, V Geldhof…
Cancer cell, 2020cell.com
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 …
Summary
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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