Simultaneous analysis of DNA, RNA and chromatin from a single cell

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Single-cell technologies measure unique cellular signatures, but are generally limited to a single modality. They work by extracting DNA, RNA or chromatin from the nucleus of a cell.

Although these methods destroy the cell in the process. Therefore, scientists must rely on computational algorithms to analyze more than one of these components per cell or compare the results.

To solve this problem, scientists at the Salk Institute have developed a new genomic technology to simultaneously analyze DNA, RNA and chromatin from a single cell. This new technology called snmCAT-seq could also better understand how genes and cells interact to cause neurodegenerative diseases.

Joseph Ecker, Director of the Genomics Analysis Laboratory, International Salk Council Chair in Genetics and Howard Hughes Medical Institute Researcher, said: “This multimodal platform will be useful in providing a comprehensive database that can be used by groups trying to integrate their single-modal data. This new information may also inform and guide the future classification of cell types.

Scientists label DNA, RNA and chromatin with biomarkers without removing them from the cell. This allowed them to measure all three types of molecular information in the same cell.

Using this method, scientists have identified 63 cell types in the frontal cortex region of the human brain. They found that the technology evaluated the efficiency of computational methods for integrating multiple single-cell technologies.

The technology could also better understand how genes and cells interact to cause neurodegenerative diseases.

Co-first author Chongyuan Luo, assistant professor of human genetics at UCLA’s David Geffen School of Medicine, noted, “These diseases can broadly affect many cell types. But some cell populations could be particularly vulnerable. Genetic research has identified regions of the genome that are relevant to diseases like Alzheimer’s disease. We provide another dimension of data and identify cell types affected by these genomic regions.

Scientists plan to use the new platform to study other areas of the brain.

Journal reference:

  1. Chongyuan Luo et al. Single-nucleus multi-omics identifies the regulatory genome diversity of human cortical cells. DO I: 10.1016/j.xgen.2022.100107
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