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
-
The SAGA complex regulates early steps in transcription via its deubiquitylase module subunit USP22NCBI Gene Expression Omnibus, GSE158081.
-
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.
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.
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.
Metrics
-
- 2,175
- views
-
- 333
- downloads
-
- 19
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Transcriptional drifts associated with environmental changes in endothelial cells
eLife 12:e81370.
https://doi.org/10.7554/eLife.81370
Further reading
-
- Cell Biology
Endometriosis is a debilitating disease affecting 190 million women worldwide and the greatest single contributor to infertility. The most broadly accepted etiology is that uterine endometrial cells retrogradely enter the peritoneum during menses, and implant and form invasive lesions in a process analogous to cancer metastasis. However, over 90% of women suffer retrograde menstruation, but only 10% develop endometriosis, and debate continues as to whether the underlying defect is endometrial or peritoneal. Processes implicated in invasion include: enhanced motility; adhesion to, and formation of gap junctions with, the target tissue. Endometrial stromal (ESCs) from 22 endometriosis patients at different disease stages show much greater invasiveness across mesothelial (or endothelial) monolayers than ESCs from 22 control subjects, which is further enhanced by the presence of EECs. This is due to the enhanced responsiveness of endometriosis ESCs to the mesothelium, which induces migration and gap junction coupling. ESC-PMC gap junction coupling is shown to be required for invasion, while coupling between PMCs enhances mesothelial barrier breakdown.
-
- Cell Biology
A combination of intermittent fasting and administering Wnt3a proteins to a bone injury can rejuvenate bone repair in aged mice.
