# A Spatially Resolved Molecular Atlas of Human Endothelium

> **NIH NIH U54** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2020 · $1,405,591

## Abstract

ABSTRACT - ORGAN SPECIFIC PROJECT (Endothelium)
The human circulatory system plays a vital role in the proper functioning of every organ in the human body.
Because vascular related diseases, such as atherosclerosis, do not occur homogeneously throughout the
vascular tree, differences in the endothelium of various organs must exist. There is even evidence of
heterogeneity of adjacent endothelial cells. We propose an Organ Specific Project (OSP) that will study normal
endothelium throughout the body and across individuals of different ages to characterize these differences.
The first step will be to procure normal tissue samples from a wide range of organs. The tissue source will be
brainstem dead donors, which allows for collection of sample with minimal ischemic time within an ethical
framework allowing for genomic data sharing. From disaggregated samples of these tissues, we will perform
single cell combinatorial indexing (sci-) to generate chromatin accessibility (sci-ATAC-seq) and transcriptome
(sci-RNA-seq) data from millions of single cells across hundreds of samples. These are established, low-cost,
scalable methods that will facilitate the identification of markers that are ubiquitous or heterogeneous in human
endothelium. Molecular heterogeneity might correlate with multiple facets of the anatomical distribution of
endothelium, including vascular vs. lymphatic, arteries vs. veins, capillaries vs. larger vessels, differences
between organs, organ zonation, cell-to-cell differences, etc. Based on heterogeneous markers defined from
deep profiling of disaggregated cells, we will employ seqFISH to spatially relate the distinct endothelial
subpopulations arising from the single nuclei data to histologic preparations. For example, this will allow us to
identify subpopulations with particular markers as arterial, capillary, venous, or lymphatic. Differences in the
transcriptome and chromatin accessibility profiles of specific endothelial subpopulations within organs, between
organs, and across ages, will be subjected to a unified, integrative analytical framework. The end product of
this integration will include multiparameter images in which the complete gene expression and chromatin
accessibility profile can be interactively visualized for every cell. The incidental collection of sci-ATAC-seq and
sci-RNA-seq data for non-endothelial cell types may be extremely useful to inform and increase the value of
the datasets collected by other TMCs and OSPs, as well as to facilitate spatial and molecular integration of the
data corresponding to endothelium with organ-specific maps. We anticipate that our spatially resolved map of
transcription and chromatin accessibility in normal endothelium in tissues throughout the body will lay the
foundation for investigating the molecular basis for vascular diseases.

## Key facts

- **NIH application ID:** 9966768
- **Project number:** 5U54HL145611-03
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Long Cai
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,405,591
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9966768

## Citation

> US National Institutes of Health, RePORTER application 9966768, A Spatially Resolved Molecular Atlas of Human Endothelium (5U54HL145611-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9966768. Licensed CC0.

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