Endothelial heterogeneity across distinct vascular beds during homeostasis and inflammation
- University of Illinois at Chicago, United States
Abstract
Blood vessels are lined by endothelial cells engaged in distinct organ-specific functions but little is known about their characteristic gene expression profiles. RNA-Sequencing of the brain, lung, and heart endothelial translatome identified specific pathways, transporters and cell-surface markers expressed in the endothelium of each organ, which can be visualized at http://www.rehmanlab.org/ribo. We found that endothelial cells express genes typically found in the surrounding tissues such as synaptic vesicle genes in the brain endothelium and cardiac contractile genes in the heart endothelium. Complementary analysis of endothelial single cell RNA-Seq data identified the molecular signature shared across the endothelial translatome and single cell transcriptomes. The tissue-specific heterogeneity of the endothelium is maintained during systemic in vivo inflammatory injury as evidenced by the distinct responses to inflammatory stimulation. Our study defines endothelial heterogeneity and plasticity and provides a molecular framework to understand organ-specific vascular disease mechanisms and therapeutic targeting of individual vascular beds.
Data availability
RNA Sequencing data have been deposited in GEO under accession code GSE136848We downloaded Tabula Muris data from https://github.com/czbiohub/tabula-muris and Betsholtz Lab data from NCBI Gene Expression Omnibus (GSE99235, GSE98816)
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Single cell RNA-seq of mouse lung vascular transcriptomesNCBI Gene Expression Omnibus, GSE99235.
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Single cell RNA-seq of mouse brain vascular transcriptomesNCBI Gene Expression Omnibus, GSE98816.
Article and author information
Author details
Funding
National Institutes of Health (R01HL126516)
- Jalees Rehman
National Institutes of Health (P01-HL60678)
- Asrar B Malik
- Jalees Rehman
National Institutes of Health (T32-HL007829)
- Asrar B Malik
National Institutes of Health (R01-HL90152)
- Asrar B Malik
- Jalees Rehman
American Heart Association (18CDA34110068)
- Lianghui Zhang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Anna Akhmanova, Utrecht University, Netherlands
Ethics
Animal experimentation: All animal experiments were conducted in accordance with NIH guidelines for the Care and Use of Laboratory Animals and were performed in accordance with protocols approved by the Institutional Animal Care and Use Committees (IACUC) of the University of Illinois (protocol approval numbers 19-014, 13-175 and 16-064) .
Version history
- Received: August 27, 2019
- Accepted: January 15, 2020
- Accepted Manuscript published: January 16, 2020 (version 1)
- Version of Record published: February 5, 2020 (version 2)
Copyright
© 2020, Jambusaria 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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Endothelial heterogeneity across distinct vascular beds during homeostasis and inflammation
eLife 9:e51413.
https://doi.org/10.7554/eLife.51413
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