Identification of Transcriptional Drifts in Endothelial Cells Associated with Environmental Changes

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 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, ATACseq, 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. In contrast, co-culture of endothelial cells with smooth muscle cells normalized approximately 9% of the original in vivo signature. Our findings highlight specific genes and pathways that rely on contextual information and physical forces.