Transcriptional drifts associated with environmental changes in endothelial cells

Abstract

Environmental cues, such as physical forces and heterotypic cell interactions play a critical role in cell function, yet their collective contributions to transcriptional changes are unclear. Focusing on human endothelial cells, we performed broad individual sample analysis to identify transcriptional drifts associated with environmental changes that were independent of genetic background. Global gene expression profiling by RNA-seq and protein expression by LC-MS directed proteomics distinguished endothelial cells in vivo from genetically matched culture (in vitro) samples. Over 43% of the transcriptome was significantly changed by the in vitro environment. Subjecting cultured cells to long-term shear stress significantly rescued the expression of approximately 17% of genes. Inclusion of heterotypic interations by co-culture of endothelial cells with smooth muscle cells normalized approximately 9% of the original in vivo signature. We identify novel flow depedent genes, as well as, genes that necessitate heterotypic cell interactions to mimic the in vivo transcriptome. Our findings highlight specific genes and pathways that rely on contextual information and physical forces.

Exploiting a Type III Interferon Response to Improve Chemotherapeutic Safety and Efficacy

“…Interestingly, we did not observe any expression of IFNLR1 in either basal state cells or cells treated with exogenous IFN-λ (Table 1). However, gene expression pro les of cultured endothelial cells are notoriously variable depending on environmental factors such as physical forces and heterotypic cell interactions 38,39 . Whether human lung microvascular endothelial cells express the IFNLR1 has not been extensively investigated, but this variability in cultured endothelial cells may explain why we do not see IFNLR1 expression in our cell culture model.…”