Multichrome Encoding-based Multiplexed, Spatially Resolved Imaging Reveals Single-cell RNA Epigenetic Modifications Heterogeneity

Overview

Journal Nat Commun

Date 2025 Jan 22

PMID 39843433

Authors

Dongsheng Mao

XiaoChen Tang

Runchi Zhang

Song Hu

Hongquan Gou

Penghui Zhang

Wenxing Li

Qiuhui Pan

Bing Shen

Xiaoli Zhu

Affiliations

Soon will be listed here.

Abstract

Understanding the heterogeneity of epigenetic modifications within single cells is pivotal for unraveling the nature of the complexity of gene expression and cellular function. In this study, we have developed a strategy based on multichrome encoding and "AND" Boolean logic recognition for multiplexed, spatially resolved imaging of single-cell RNA epigenetic modifications, termed as PRoximity Exchange-assisted Encoding of Multichrome (PREEM). Through the implementation of this strategy, we can now map the expression and nuclear distribution of multiple site-specific RNA N6-methyladenosine (mA) modifications at the single-molecule resolution level in single-cells, and reveal the previously unknown heterogeneity. Notably, we demonstrate how these patterns change after treatment with various drugs. Moreover, cyclic imaging with tailed DNA self-assembly further suggest the scalability and adaptability of PREEM's design. As an innovative epigenetic modification imaging tool, PREEM not only broadens the horizons of single-cell epigenetics research, enabling joint analysis of multiple targets beyond the limitations of imaging channels, but also reveals cell-to-cell variability, thereby enhancing our capacity to explore cellular functions.

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