# Single cell analysis of gene expression in human vascular cells

> **NIH NIH R03** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $89,500

## Abstract

Project Summary
In my clinical training, I repeatedly saw the devastating effects of vascular disease on
patients in the prime of their lives. Vascular diseases such as coronary artery disease
(CAD), stroke, arterial dissection, and migraine headache combine to cause over half the
death and disability in the United States. To eradicate vascular disease it will be important
to develop new treatments that target the arterial cells where the disease begins. My K08-
funded research has been to identify these new pathways using human genetic variation
as a guide. The loci associated with multiple vascular diseases have recently been
identified through genome-wide association studies (GWAS). These loci represent new
therapeutic targets, but their biological mechanisms remain largely unexplored. I have
identified the mechanism by which a vascular disease associated variant on chromosome
6p24 distally regulates endothelin-1 expression. This regulatory effect of the non-coding
variant is vascular tissue specific, and largely seen in endothelial cells. Whether other
cells in the blood vessel are responsible for other gene regulatory effects for this locus
remains unknown. For this and other vascular disease-associated loci it will be important
to characterize the gene regulatory effects in the relevant cell type or cellular
subpopulation. New methods in single cell RNA-sequencing all the identification of the
full set of cells in the arterial wall. Droplet-based single cell RNA-sequencing allows for
analysis of thousands of cells and detection of rare cellular subpopulations. Using this
method, I have identified three distinct subpopulations of endothelial cells with
transcriptional signatures that suggest functional specialization. This R03 application
seeks to extend this finding to human vascular tissue. The goals of this proposal are to
determine the best method for single cell RNA-sequencing and to determine the markers
of endothelial cell heterogeneity in human vascular tissue. This will provide an atlas of
cell types based on transcriptional signature in vascular tissue and serve as a
foundational resource for future functional genomics experiments. With a better
understanding of the cell types and gene expression signatures in the arterial wall it will
be possible to identify new biological pathways for the treatment and prevention of
vascular disease.

## Key facts

- **NIH application ID:** 9987754
- **Project number:** 5R03HL148483-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** RAJAT M GUPTA
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $89,500
- **Award type:** 5
- **Project period:** 2019-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987754

## Citation

> US National Institutes of Health, RePORTER application 9987754, Single cell analysis of gene expression in human vascular cells (5R03HL148483-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9987754. Licensed CC0.

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