# Expansion genomics for high-resolution single-cell and spatial epigenomics

> **NIH NIH R01** · HARVARD UNIVERSITY · 2024 · $743,524

## Abstract

Project Summary
The diversity of cell states observed across development, aging, and disease is regulated by the epigenome, an
intricate medley of chromatin states, chemical modifications, protein interactions, and three-dimensional
structures in the nucleus. We and others have developed techniques such as ATAC-seq, CUT&Tag, and In situ
Genome Sequencing (IGS) that use Tn5 transposase to selectively measure different components of the
epigenome, increasingly at single-cell resolution. However, these techniques all suffer from poor yield due to an
inherent challenge: the amount of physical space available for enzymatic reactions in the nucleus is limited. To
address this challenge, we propose a new platform called Expansion Genomics, which will leverage physical
expansion of biological samples to de-crowd the nucleus, vastly increasing the resolution of single-cell and
spatial epigenomics methods. In Aim 1, we describe Single-cell Expansion Genomics, which will combine
expansion with modern single-cell techniques to enable high-throughput, multi-modal measurements without the
need for specialized microfluidic devices. In Aim 2, we describe Spatial Expansion Genomics, which will integrate
expansion with multiplexed spatial imaging approaches to reveal the organization of the epigenome at
nanoscale. These technologies will be designed with ease and accessibility as a guiding principle to facilitate
widespread adoption and broaden our understanding of gene regulatory mechanisms.

## Key facts

- **NIH application ID:** 10945335
- **Project number:** 1R01HG013679-01
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Jason Daniel Buenrostro
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $743,524
- **Award type:** 1
- **Project period:** 2024-09-19 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10945335

## Citation

> US National Institutes of Health, RePORTER application 10945335, Expansion genomics for high-resolution single-cell and spatial epigenomics (1R01HG013679-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10945335. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*