Bulk and single-cell alternative splicing analyses reveal roles of TRA2B in myogenic differentiation

文献类型： 外文期刊

第一作者： Chen, Genghua

作者： Chen, Genghua;Chen, Jiahui;Qi, Lin;Yin, Yunqian;Lin, Zetong;Wen, Huaqiang;Zhang, Shuai;Bello, Semiu Folaniyi;Zhang, Xiquan;Nie, Qinghua;Luo, Wen;Chen, Genghua;Chen, Jiahui;Qi, Lin;Yin, Yunqian;Lin, Zetong;Wen, Huaqiang;Zhang, Shuai;Bello, Semiu Folaniyi;Zhang, Xiquan;Nie, Qinghua;Luo, Wen;Chen, Genghua;Chen, Jiahui;Qi, Lin;Yin, Yunqian;Lin, Zetong;Wen, Huaqiang;Zhang, Shuai;Bello, Semiu Folaniyi;Zhang, Xiquan;Nie, Qinghua;Luo, Wen;Chen, Genghua;Chen, Jiahui;Qi, Lin;Yin, Yunqian;Lin, Zetong;Wen, Huaqiang;Zhang, Shuai;Bello, Semiu Folaniyi;Zhang, Xiquan;Nie, Qinghua;Luo, Wen;Chen, Genghua;Chen, Jiahui;Qi, Lin;Yin, Yunqian;Lin, Zetong;Wen, Huaqiang;Zhang, Shuai;Bello, Semiu Folaniyi;Zhang, Xiquan;Nie, Qinghua;Luo, Wen;Xiao, Chuanyun;Nie, Qinghua;Luo, Wen

作者机构：

期刊名称：CELL PROLIFERATION （ 影响因子：8.5； 五年影响因子：7.8 ）

ISSN： 0960-7722

年卷期： 2023 年

页码：

收录情况： SCI

摘要： Alternative splicing (AS) disruption has been linked to disorders of muscle development, as well as muscular atrophy. However, the precise changes in AS patterns that occur during myogenesis are not well understood. Here, we employed isoform long-reads RNA-seq (Iso-seq) and single-cell RNA-seq (scRNA-seq) to investigate the AS landscape during myogenesis. Our Iso-seq data identified 61,146 full-length isoforms representing 11,682 expressed genes, of which over 52% were novel. We identified 38,022 AS events, with most of these events altering coding sequences and exhibiting stage-specific splicing patterns. We identified AS dynamics in different types of muscle cells through scRNA-seq analysis, revealing genes essential for the contractile muscle system and cytoskeleton that undergo differential splicing across cell types. Gene-splicing analysis demonstrated that AS acts as a regulator, independent of changes in overall gene expression. Two isoforms of splicing factor TRA2B play distinct roles in myogenic differentiation by triggering AS of TGFBR2 to regulate canonical TGF-beta signalling cascades differently. Our study provides a valuable transcriptome resource for myogenesis and reveals the complexity of AS and its regulation during myogenesis.

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