Wang Wei, Zhang Yu, Zhai Yuanyuan, Yang Wuritu, Xing Yongqiang
Inner Mongolia Key Laboratory of Life Health and Bioinformatics, School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, China.
Computer Department, Hohhot Vocational College, Hohhot, China.
Sci Rep. 2025 Mar 31;15(1):10948. doi: 10.1038/s41598-025-96148-7.
Alternative splicing (AS) plays an essential role in development, differentiation and carcinogenesis. However, the mechanisms underlying splicing regulation during mouse embryo gastrulation remain unclear. Based on spatial-temporal transcriptome and epigenome data, we detected the dynamics of AS and revealed its regulatory mechanisms across primary germ layers during mouse gastrulation, spanning developmental stages from E6.5 to E7.5. Subsequently, the dynamic expression of splicing factors (SFs) during gastrulation was characterized, while the expression patterns and functions of germ layer-specific SFs were identified. The results indicate that AS and differential alternative splicing events (DASEs) exhibit dynamic changes and are significantly abundant during the late stage of gastrulation. Similarly, SFs demonstrate stage-specific expression, with elevated levels observed during the middle and late stages of gastrulation. Epigenetic signals associated with SFs and AS sites demonstrate significant enrichment and undergo dynamic changes throughout gastrulation. Overall, this study offers a systematic analysis of AS during mouse gastrulation, identifies primary germ layer-specific AS events, and characterizes the expression patterns of SFs and the associated epigenetic signals. These findings enhance the understanding of the mechanisms underlying the formation of the three germ layers during mammalian gastrulation, with a focus on pre-mRNA AS.
可变剪接(AS)在发育、分化和致癌过程中起着至关重要的作用。然而,小鼠胚胎原肠胚形成过程中剪接调控的潜在机制仍不清楚。基于时空转录组和表观基因组数据,我们检测了AS的动态变化,并揭示了其在小鼠原肠胚形成过程中跨越三个原始胚层(从E6.5到E7.5发育阶段)的调控机制。随后,我们对原肠胚形成过程中剪接因子(SFs)的动态表达进行了表征,同时鉴定了胚层特异性SFs的表达模式和功能。结果表明,AS和差异可变剪接事件(DASEs)呈现动态变化,并且在原肠胚形成后期显著丰富。同样,SFs表现出阶段特异性表达,在原肠胚形成的中期和后期水平升高。与SFs和AS位点相关的表观遗传信号在整个原肠胚形成过程中表现出显著富集并经历动态变化。总体而言,本研究对小鼠原肠胚形成过程中的AS进行了系统分析,鉴定了原始胚层特异性AS事件,并表征了SFs的表达模式和相关的表观遗传信号。这些发现加深了我们对哺乳动物原肠胚形成过程中三个胚层形成机制的理解,重点是前体mRNA的可变剪接。