# High-throughput analysis of the effects of gene promoters and chromosomal environments on single-cell gene expression

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $411,855

## Abstract

Project Summary/Abstract
Genetically identical cells in the same environment can have large individual differences in gene
expression. This “single-cell variability” in gene expression diversifies cell types during development,
contributes to chemotherapeutic resistance in cancer cells, and hinders the production of pure cell types
in reprogramming protocols. Although single-cell variability is an important property of gene expression in
development and disease, the sequence features of promoters and the epigenetic features of
chromosomes that predict a gene’s single-cell variability are unknown. To address this gap, we propose
to develop a high-throughput technology that measures the single-cell variability of different classes of
promoters in diverse chromosomal environments. We propose to integrate transgenes into thousands of
locations across the genome and measure the resulting single-cell variability of transgene expression from
all locations in parallel. These data will allow us to leverage existing epigenomic maps to identify the
features of chromosomal environments that amplify or dampen single-cell variability in gene expression.
We propose to apply this technology to multiple cell types and with transgenes carrying diverse promoters.
The resulting data will be analyzed with a framework separates the independent contributions of promoters
and chromosomal environments to single-cell variability, and also quantifies any interactions between
specific promoters and chromosomal environments that impact single-cell variability. Our goal in
developing this technology is to understand the properties of the genome that control the single-cell
variability of mRNA expression.

## Key facts

- **NIH application ID:** 10766767
- **Project number:** 5R01HG012304-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Barak A Cohen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $411,855
- **Award type:** 5
- **Project period:** 2022-02-16 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10766767

## Citation

> US National Institutes of Health, RePORTER application 10766767, High-throughput analysis of the effects of gene promoters and chromosomal environments on single-cell gene expression (5R01HG012304-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10766767. Licensed CC0.

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