Transcriptional drifts associated with environmental changes in endothelial cells

Yalda Afshar, Feiyang Ma, Austin Quach, Anhyo Jeong, Hannah Louise Sunshine, Vanessa Freitas, Yasaman Jami-Alahmadi, Raphael Helaers, Xinmin Li, Matteo Pellegrini, James Wohlschlegel, Casey E. Romanoski, Miikka Vikkula, M. Luisa Iruela-Arispe

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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 RNAseq 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 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.

Original languageEnglish (US)
Article numbere81370
JournaleLife
Volume12
DOIs
StatePublished - Mar 2023

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

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