Simultaneous profiling of RNA isoforms and chromatin accessibility of single cells of human retinal organoids

Shuyao Zhang, Yuhua Xiao, Xinzhi Mo, Xu Chen, Jiawei Zhong, Zheyao Chen, Xu Liu, Yuanhui Qiu, Wangxuan Dai, Jia Chen, Xishan Jin, Guoping Fan and Youjin Hu ()
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Shuyao Zhang: Sun Yat-Sen University
Yuhua Xiao: Sun Yat-Sen University
Xinzhi Mo: Sun Yat-Sen University
Xu Chen: Sun Yat-Sen University
Jiawei Zhong: Sun Yat-Sen University
Zheyao Chen: Sun Yat-Sen University
Xu Liu: Sun Yat-Sen University
Yuanhui Qiu: Sun Yat-Sen University
Wangxuan Dai: Sun Yat-Sen University
Jia Chen: Sun Yat-Sen University
Xishan Jin: Sun Yat-Sen University
Guoping Fan: UCLA
Youjin Hu: Sun Yat-Sen University

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract Single-cell multi-omics sequencing is a powerful approach to analyze complex mechanisms underlying neuronal development and regeneration. However, current methods lack the ability to simultaneously profile RNA alternative splicing and chromatin accessibility at the single-cell level. We develop a technique, single-cell RNA isoform and chromatin accessibility sequencing (scRICA-seq), which demonstrates higher sensitivity and cost-effectiveness compared to existing methods. scRICA-seq can profile both isoforms and chromatin accessibility for up to 10,000 single cells in a single run. Applying this method to human retinal organoids, we construct a multi-omic cell atlas and reveal associations between chromatin accessibility, isoform expression of fate-determining factors, and alternative splicing events in their binding sites. This study provides insights into integrating epigenetics, transcription, and RNA splicing to elucidate the mechanisms underlying retinal neuronal development and fate determination.

Date: 2024
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DOI: 10.1038/s41467-024-52335-0

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