Chen Jiwei, Wei Gaigai, Sun Fangge, Li Yunjin, Tang Shuang, Chen Geng
Center for Bioinformatics and Computational Biology, and Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences, School of Life Sciences, East China Normal University Shanghai China.
Cancer Institute Fudan University Shanghai Cancer Center Shanghai China.
FASEB Bioadv. 2025 Jul 9;7(7):e70036. doi: 10.1096/fba.2025-00075. eCollection 2025 Jul.
Single-cell RNA-seq (scRNA-seq) technologies greatly revolutionized our understanding of cell-to-cell variability of gene expression, but few scRNA-seq technologies were used to describe the expression dynamics at the isoform and exon levels. Although the current expression profile of early embryos was studied focusing on the expression changes at the gene level, systematic investigation of gene expression dynamics of human early embryonic development remains insufficient. Here we systematically explored the gene expression dynamics of human early embryonic development integrating gene expression level with alternative splicing, isoform switching, and expression regulatory network. We found that the genes involved in significant changes in these three aspects are all gradually decreased along embryonic development from E3 to E7 stage. Moreover, these three types of variations are complementary for profiling expression dynamics, and they vary significantly across embryonic development as well as between different sexes. Strikingly, only a small number of genes exhibited prominent expression level changes between male and female embryos in the E3 stage, whereas many more genes showed variations in alternative splicing and major isoform switching. Additionally, we identified functionally important specific gene regulatory modules for each stage and revealed dynamic usage of transcription factor binding motifs (TFBMs). In conclusion, this study provides informative insights into gene dynamic characteristics of human early embryonic development by integrating gene expression level with alternative splicing, isoform switching, and gene regulatory networks. A systematic understanding of gene dynamic alteration features during embryonic development not only expands knowledge on basic developmental biology but also provides fundamental insights for regenerative medicine and developmental diseases.
单细胞RNA测序（scRNA-seq）技术极大地革新了我们对基因表达细胞间变异性的理解，但很少有scRNA-seq技术用于描述异构体和外显子水平的表达动态。尽管目前对早期胚胎的表达谱进行了研究，重点关注基因水平的表达变化，但对人类早期胚胎发育基因表达动态的系统研究仍然不足。在这里，我们系统地探索了人类早期胚胎发育的基因表达动态，将基因表达水平与可变剪接、异构体切换和表达调控网络相结合。我们发现，参与这三个方面显著变化的基因在从E3到E7阶段的胚胎发育过程中均逐渐减少。此外，这三种类型的变异在描述表达动态方面具有互补性，它们在胚胎发育过程中以及不同性别之间存在显著差异。引人注目的是，在E3阶段，只有少数基因在雄性和雌性胚胎之间表现出显著的表达水平变化，而更多的基因在可变剪接和主要异构体切换方面表现出差异。此外，我们确定了每个阶段功能上重要的特定基因调控模块，并揭示了转录因子结合基序（TFBMs）的动态使用情况。总之，本研究通过将基因表达水平与可变剪接、异构体切换和基因调控网络相结合，为人类早期胚胎发育的基因动态特征提供了丰富的见解。对胚胎发育过程中基因动态改变特征的系统理解不仅扩展了基础发育生物学的知识，也为再生医学和发育疾病提供了基本见解。
