Tian Geng G, Li Jing, Wu Ji
1Renji Hospital, Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240 China.
3Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240 China.
Cell Biosci. 2020 Mar 10;10:33. doi: 10.1186/s13578-020-00399-y. eCollection 2020.
Preimplantation embryo development is a highly ordered sequence of processes and it requires a precise temporal and spatial control of gene expression. Alternative splicing (AS) is a crucial process that changes the genomic instructions into functional proteins, playing a critical role in the regulation of gene expression. Therefore, studies of AS can significantly improve our understanding of transcription and splicing events in preimplantation embryo development.
To study signatures of AS in embryo development, we firstly identified the critical stage for gene transcription during the preimplantation embryo development. By analyzing single cells RNA-seq (scRNA-seq) data, we found that the two-cell stage is a critical stage for gene transcription in preimplantation embryo development. Further study showed that AS was widespread in preimplantation embryo development, especially at the two-cell stage. In combination with high-throughput chromosome conformation (Hi-C) data, we demonstrated that AS genes were highly enriched in TAD boundaries, while they had no relationship with the A/B compartment and TAD.
Our results provide new insight into the relationship among AS, gene transcription and chromatin structure in preimplantation embryo development.
植入前胚胎发育是一系列高度有序的过程，需要对基因表达进行精确的时空控制。可变剪接（AS）是一个关键过程，它将基因组指令转化为功能蛋白，在基因表达调控中发挥关键作用。因此，对可变剪接的研究可以显著提高我们对植入前胚胎发育中转录和剪接事件的理解。
为了研究胚胎发育中可变剪接的特征，我们首先确定了植入前胚胎发育过程中基因转录的关键阶段。通过分析单细胞RNA测序（scRNA-seq）数据，我们发现二细胞阶段是植入前胚胎发育中基因转录的关键阶段。进一步研究表明，可变剪接在植入前胚胎发育中广泛存在，尤其是在二细胞阶段。结合高通量染色体构象（Hi-C）数据，我们证明可变剪接基因在拓扑相关结构域（TAD）边界高度富集，而它们与A/B区室和TAD无关。
我们的结果为植入前胚胎发育中可变剪接、基因转录和染色质结构之间的关系提供了新的见解。
