Transcriptomics

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An integrated approach to profile lung tumor endothelial cell heterogeneity across species and models and to identify angiogenic candidates


ABSTRACT: Heterogeneity of lung tumor endothelial cell (TEC) phenotypes across patients, species (human/mouse) and models (in vivo/vitro) remains poorly inventoried at the single-cell-level. We single-cell RNA-sequenced 56,771 ECs from human/mouse (peri)-tumoral lung and cultured human lung TECs, detected 17 known and discovered 16 novel phenotypes, including TECs presumably regulating immune surveillance. We resolved the canonical tip TECs into a known migratory tip and a novel basement-membrane remodeling breach phenotype. Tip-TEC signatures correlated with patient-survival, and tip/breach TECs were most sensitive to VEGF-blockade. By similarity analysis, only tip-TECs were congruent across species/models and shared conserved markers. Integrated analysis of the scRNA-seq data with orthogonal multi-omics and meta-analysis data across different human tumors, validated by functional analysis, identified collagen-modification as angiogenic candidate pathway.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Homo sapiens  

SUBMITTER: Shawez Khan  

PROVIDER: E-MTAB-6308 | ArrayExpress | 2019-12-30

SECONDARY ACCESSION(S): ERP118248

REPOSITORIES: ArrayExpress, ENA

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