Cardiac endothelial cells maintain open chromatin and expression of cardiomyocyte myofibrillar genes
- University of Pennsylvania, United States
Abstract
Endothelial cells (ECs) are widely heterogenous depending on tissue and vascular localization. Jambusaria et al. recently demonstrated that ECs in various tissues surprisingly possess mRNA signatures of their underlying parenchyma. The mechanism underlying this observation remains unexplained, and could include mRNA contamination during cell isolation, in vivo mRNA paracrine transfer from parenchymal cells to ECs, or cell-autonomous expression of these mRNAs in ECs. Here, we use a combination of bulk RNASeq, single cell RNASeq datasets, in situ mRNA hybridization, and most importantly ATAC-Seq of FACS-isolated nuclei, to show that cardiac endothelial cells actively express cardiomyocyte myofibril (CMF) genes and have open chromatin at CMF gene promoters. These open chromatin sites are enriched for sites targeted by cardiac transcription factors, and close upon expansion of ECs in culture. Together, these data demonstrate unambiguously that the expression of CMF genes in ECs is cell-autonomous, and not simply a result of technical contamination or paracrine transfers of mRNAs, and indicate that local cues in the heart in vivo unexpectedly maintain fully open chromatin in ECs at genes previously thought limited to cardiomyocytes.
Data availability
Sequencing data have been deposited in GEO under accession number GSE144839.
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Cardiac endothelial cells maintain open chromatin and expresion of cardiomyocyte myofibrillar genesNCBI Gene Expression Omnibus, GSE144839.
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The in vivo endothelial cell translatome is highly heterogeneous across vascular bedsNCBI Gene Expression Omnibus, GSE138630.
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Meox2/Tcf15 heterodimers program the heart capillary endothelium for cardiac fatty acid uptakeNCBI Gene Expression Omnibus, GSE48209.
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Human Organ-Specific Endothelial Cell HeterogeneityNCBI Gene Expression Omnibus, GSE114607.
Article and author information
Author details
Funding
National Institute of Diabetes and Digestive and Kidney Diseases (R01HLDK114103)
- Zoltan Arany
American Heart Association (AHA/Allen Initative)
- Zoltan Arany
National Institutes of Health (T32 DKO7314)
- Nora Yucel
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#805255) of the University of Pennsylvania.
Copyright
© 2020, Yucel 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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Cardiac endothelial cells maintain open chromatin and expression of cardiomyocyte myofibrillar genes
eLife 9:e55730.
https://doi.org/10.7554/eLife.55730
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