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

Abstract

Highlights d We single-cell RNA-sequenced 56,771 endothelial cells (ECs) from human, mouse, and cultured lung tumor models d Tip ECs were resolved into migratory and basementmembrane remodeling phenotypes d Capillary and venous ECs expressed immunoregulatory gene signatures d Integrated analysis identified collagen modification as an angiogenic pathway

Endothelial-to-Mesenchymal Transition in Cancer

“…Intermediate stages of differentiation in tumors-derived ECs have been identified (Xiao et al, 2015) and these tumor ECs display heterogeneity in their potentiality to undergo EndMT. This is consistent with the phenotypic heterogeneity of ECs in tumors (Maishi et al, 2019;Goveia et al, 2020), combined with the diversity of signals emanating from TME, as fine tuning of EndMT appears to be under the control of several factors such as transforming growth factor-β (TGF-β) and basic fibroblast growth factor (bFGF) (Xiao and Dudley, 2017). Moreover, partial EndMT has been assimilated as an initial step of endothelial sprouting in angiogenesis process (Welch-Reardon et al, 2015;Wang et al, 2017).…”

Hierarchical imaging and computational analysis of three-dimensional vascular network architecture in the entire postnatal and adult mouse brain

“…Moreover, there is also a lack of reliable capillary markers 142–145 which otherwise might solve this issue for staining-based methods. Indeed, markers for capillary endothelial have been proposed in recent years, for instance, Mfsd2a 154 , TFRC, SKC16a2, CA4, CXCL12, Rgcc, SPOCK2 and others that were recently identified in large endothelial single-cell-RNA sequencing datasets 155–157 . However, to the best of our knowledge, there is currently no established cellular marker that selectively labels capillaries, as all the proposed and above-mentioned markers also label non-capillary blood vessels, even though to a lesser extent 156,157 .…”

“…Indeed, markers for capillary endothelial have been proposed in recent years, for instance, Mfsd2a 154 , TFRC, SKC16a2, CA4, CXCL12, Rgcc, SPOCK2 and others that were recently identified in large endothelial single-cell-RNA sequencing datasets 155–157 . However, to the best of our knowledge, there is currently no established cellular marker that selectively labels capillaries, as all the proposed and above-mentioned markers also label non-capillary blood vessels, even though to a lesser extent 156,157 . Accordingly, the most adequate method for distinguishing capillary and non-capillary blood vessels is still based on the morphological criteria of the inner vessel diameter, e.g.…”

Unraveling the Complexity of the Cancer Microenvironment With Multidimensional Genomic and Cytometric Technologies

“…Several studies have applied mass cytometry to further characterize immune cell profiles in peripheral blood or tissues from patients with breast cancer (101), renal cancer (102), melanoma (55,56,(103)(104)(105), lung cancer (52,106,107), glioma (49,50), colorectal cancer (57,106,108,109), liver cancer (61,110), ovarian cancer (111), and myeloma (112)(113)(114)(115), among others. In addition to characterizing immune cell profiles of different tissue types, mass cytometry has also been used to characterize immunophenotypes in tumors and monitor changes during immunotherapy (56,(103)(104)(105)114).…”

“…Notably, all different multidimensional datasets in these studies were analyzed separately and follow a late (model-based) stage integration. Only Goveia and colleagues applied an integration of clustered mass cytometry and scRNA-seq data (107). They merged scaled average gene expression data for each scRNAseq cluster with scaled average protein expression data for each CyTOF cluster, an approach based on a recently described method from Giordani et al (167).…”