# Integrative single-cell spatial genomic, transcriptomic, and epigenetic imaging in mammalian tissue

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $545,280

## Abstract

Project Summary/Abstract
The three-dimensional (3D) organization of the genome affects many genomic functions. Multiple 3D genome
architectures at different length scales, including chromatin loops, domains, compartments, and regions
associated with nuclear lamina and nucleoli, have been discovered. Changes in these architectures have been
associated with normal development, aging, and a wide range of diseases. However, how these structures are
arranged in the same cell, how they vary in different cell types in mammalian tissue, and how they are
correlated with gene expression and the epigenome in the tissue contexts are largely unknown. Current
approaches are severely limited by a lack of capacity to simultaneously trace chromatin folding across multiple
length scales, measure genomic organization in relation to other nuclear components, and profile gene
expression and epigenome in the same single cells in mammalian tissue. To address this need, here we
propose to develop a new methodology, termed Multiplexed Imaging of Nucleome Architectures (MINA), which
will enable simultaneous measurements of multiscale chromatin folding, associations of genomic regions with
nuclear lamina, nucleoli and other nuclear/epigenetic components, and copy numbers of numerous RNA
species in the same, single cells in mammalian tissue. We expect this development to broadly impact many
lines of research on 3D genomics by depicting cell-type-specific multiscale genomic architectures associated
with gene expression and epigenome, in different types of tissue undergoing different biological processes.
Furthermore, by allowing measurements within the same cell, it will in future be possible to directly test the
causal relationship between genomic architecture and gene expression, thus opening up a completely new
experimental paradigm to identify novel mechanisms that regulate gene expression across human
development, health and disease.

## Key facts

- **NIH application ID:** 10233891
- **Project number:** 5R01HG011245-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Siyuan Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $545,280
- **Award type:** 5
- **Project period:** 2020-08-10 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10233891

## Citation

> US National Institutes of Health, RePORTER application 10233891, Integrative single-cell spatial genomic, transcriptomic, and epigenetic imaging in mammalian tissue (5R01HG011245-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10233891. Licensed CC0.

---

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