Transcriptional drifts associated with environmental changes in endothelial cells

Autor: Yalda Afshar, Feyiang Ma, Austin Quach, Anhyo Jeong, Hannah L Sunshine, Vanessa Freitas, Yasaman Jami-Alahmadi, Raphael Helaers, Xinmin Li, Matteo Pellegrini, James A Wohlschlegel, Casey E Romanoski, Miikka Vikkula, M Luisa Iruela-Arispe
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: eLife, Vol 12 (2023)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.81370
Popis: 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 sequencing and protein expression by liquid chromatography–mass spectrometry 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 interactions by co-culture of endothelial cells with smooth muscle cells normalized approximately 9% of the original in vivo signature. We also identified novel flow dependent 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 for adequate expression from those that are agnostic of such environmental cues.
Databáze: Directory of Open Access Journals