I-13: Transcriptome Dynamics of Human and Mouse Preimplantation Embryos Revealed by Single Cell RNA-Sequencing

Background: Mammalian preimplantation development is a complex process involving dramatic changes in the transcriptional architecture. However, it is still unclear about the crucial transcriptional network and key hub genes that regulate the proceeding of preimplantation embryos. Materials and Methods: Through single-cell RNAsequencing (RNA-seq) of both human and mouse preimplantation embryos, we performed a comprehensive analysis of transcriptome dynamics from oocyte to morula embryos. Using the tool of bioinformatics such as weighted gene co-expression network analysis (WGCNA), we define the genetic programs and regulatory networks in preimplantation development. Results: We found that each developmental stage can be concisely delineated by a small number of functional modules of co-expressed genes that are involved in the pathways of cell cycle, gene regulation, protein translation, and metabolism and mitochondrial function, respectively. Cross-species comparisons reveal that the majority of human stage-specific modules (7 out of 9) are remarkably preserved, only to diverge in developmental specificity and timing in mice. Our results shed light on the gene regulatory mechanism underlying progressive development of mammalian early embryos. Conclusion: We have identified conserved key genes in human and mouse embryos that drive mammalian preimplantation development. When compared to exome or genomic sequencing of individual blastomeres, RNA-seq has the advantage of quantifying gene expression defects due to either genetic or epigenetic alterations. We suggest that single cell RNA-seq of a blastomere would be a valuable approach in parallel with other well established preimplantation genetic diagnosis methods.