New scHiCAR tool maps cell layers at once for 22 cell types in Duke University study

A new tool called scHiCAR can now map three layers of cell information at the same time, giving a much clearer picture than older methods.
By Newsroom | Science, Health |

Researchers have developed a new method, dubbed scHiCAR, that allows for the simultaneous examination of a cell's gene expression, its epigenetic marks, and its three-dimensional genome structure. This "trimodal" profiling within individual cells marks a significant advance, offering a more granular look at the complex machinery driving cellular function and disease.

The development promises to illuminate how these different molecular layers interact in real-time, especially during critical biological processes. Early applications have focused on brain tissue and the regeneration of muscle stem cells, revealing distinct operational principles across 22 major cell types. This integrated approach tackles a persistent challenge: the difficulty in accurately observing these molecular changes at the single-cell level with prior technologies.

Simultaneously decoding the transcriptome, epigenome and 3D genome within a single cell - 1

scHiCAR integrates transcriptome, epigenome, and 3D genome data from the same cell. This contrasts with older methods that often relied on bulk-cell data, averaging out individual cellular states and losing critical resolution. The technique has demonstrated robustness, even in challenging tissues like skeletal muscle, during processes such as muscle stem cell regeneration.

The method is presented as a scalable, efficient, and cost-effective platform for studying gene regulatory landscapes. Code for processing scHiCAR data and related tools has been made available in a GitHub repository.

Simultaneously decoding the transcriptome, epigenome and 3D genome within a single cell - 2

Mapping Molecular Interactions

The scHiCAR technology builds upon previous efforts in single-cell genomics. While some methods can profile transcriptional activity and chromatin accessibility together, they lack data on chromatin interactions. scHiCAR aims to fill this gap by more efficiently capturing long-range interactions anchored at specific regulatory elements.

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Simultaneously decoding the transcriptome, epigenome and 3D genome within a single cell - 3

"The origin of many diseases begins at the cellular level and involves multiple molecular interactions."

This integrated view is crucial for understanding the genesis of diseases, which often involve intricate cellular-level disruptions. The researchers have likened the technology's capability to "zooming in on Earth using Google Earth," implying a layered and detailed exploration of the cellular genome.

Collaboration and Availability

The development of scHiCAR is attributed to a collaboration between researchers at KAIST, led by Professor Inkyung Jung, and Duke University, under Professor Yarui Diao. The research has been published, with a DOI of 10.1038/s41585-026-03013-7. Data related to the technology, including for cell lines, is available via the GEO database under accession number GSE267117.

Background

Understanding the 3D organization of cis-regulatory elements (CREs) is considered central to controlling gene transcription. Previous single-cell 3D genome methods have faced limitations in efficiently enriching long-range cis-interactions, particularly those anchored at candidate CREs (cCREs). The development of scHiCAR seeks to overcome these limitations, providing a more comprehensive view of gene regulation dynamics.

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Other related single-cell multi-omic approaches, such as ChAIR, have also been developed, capable of simultaneously capturing chromatin accessibility (ChAIR-ATAC), 3D chromatin structure (ChAIR-PET), and gene expression (ChAIR-RNA) in individual cells. These systems have generated large datasets, processing over 100,000 single cells per experiment.

Frequently Asked Questions

Q: What is the new scHiCAR tool developed by Duke University researchers?
scHiCAR is a new method that can look at a cell's gene expression, epigenetic marks, and 3D genome structure all at the same time. This gives a very detailed view of how cells work.
Q: How does scHiCAR help us understand cells better?
scHiCAR helps scientists see how different parts of a cell work together in real-time. This is important for understanding how cells function and what goes wrong in diseases.
Q: What kind of tissues has scHiCAR been used on?
Early tests of scHiCAR have been done on brain tissue and muscle stem cells. It has helped scientists study 22 major types of cells and how they regenerate.
Q: Why is scHiCAR better than older methods for studying cells?
Older methods often looked at many cells together, which hid details about single cells. scHiCAR looks at each cell one by one, giving a much clearer and more accurate picture of cell activity.
Q: Who worked on developing the scHiCAR tool?
The scHiCAR tool was created by scientists from KAIST, led by Professor Inkyung Jung, and Duke University, led by Professor Yarui Diao.