Transcriptional drifts associated with environmental changes in endothelial cells
- University of California, Los Angeles, United States
- Northwestern University, United States
- University of São Paulo, Brazil
- University of Louvain, Belgium
- University of Arizona, United States
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file, Source Data files have been provided
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The SAGA complex regulates early steps in transcription via its deubiquitylase module subunit USP22NCBI Gene Expression Omnibus, GSE158081.
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CENP-C Cut&Run-seqNCBI Gene Expression Omnibus,GSE156939.
Article and author information
Author details
Yasaman Jami-Alahmadi
M Luisa Iruela-Arispe
Funding
National Institutes of Health (R35HL140014)
- M Luisa Iruela-Arispe
National Institutes of Health (R01HL147187)
- Casey E Romanoski
Foundation for the National Institutes of Health (FAPESP 2016/19968-3)
- Vanessa Freitas
National Institutes of Health (K12 HD000849)
- Yalda Afshar
National Institutes of Health (T32HL069766)
- Yalda Afshar
Fondation Leducq (21CVD03)
- Miikka Vikkula
- M Luisa Iruela-Arispe
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Ilse S Daehn, Icahn School of Medicine at Mount Sinai, United States
Ethics
Human subjects: Human umbilical cords were collected under Institutional Review Board (UCLA IRB#16-001694) at time of the delivery and processed 2-4 hours from time of birth. All samples were collected from patients who provided signed informed consent.
Version history
- Received: June 24, 2022
- Preprint posted: July 9, 2022 (view preprint)
- Accepted: March 26, 2023
- Accepted Manuscript published: March 27, 2023 (version 1)
- Accepted Manuscript updated: March 29, 2023 (version 2)
- Version of Record published: May 9, 2023 (version 3)
Copyright
© 2023, Afshar et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Transcriptional drifts associated with environmental changes in endothelial cells
eLife 12:e81370.
https://doi.org/10.7554/eLife.81370
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