Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing

Single-cell RNA sequencing and weighted gene co-expression network analysis are used to study transcriptome change in pre-implantation embryos and oocytes; this reveals a conserved genetic program between human and mouse but with different developmental specificity and timing, and conserved hub genes that may be key in pre-implantation development. This study of early embryonic development uses single-cell RNA sequencing and weighted gene co-expression network analysis (WGCNA) to obtain a detailed gene expression profile of human and mouse pre-implantation embryos and oocytes. The authors identify a small number of key functional modules that shape a sequential order of transcriptional changes in various pathways. They also found key hub genes that are conserved between human and mouse networks and argue that these genes may be key players in driving mammalian pre-implantation. Mammalian pre-implantation development is a complex process involving dramatic changes in the transcriptional architecture1,2,3,4. We report here a comprehensive analysis of transcriptome dynamics from oocyte to morula in both human and mouse embryos, using single-cell RNA sequencing. Based on single-nucleotide variants in human blastomere messenger RNAs and paternal-specific single-nucleotide polymorphisms, we identify novel stage-specific monoallelic expression patterns for a significant portion of polymorphic gene transcripts (25 to 53%). By weighted gene co-expression network analysis5,6, we find that each developmental stage can be delineated concisely by a small number of functional modules of co-expressed genes. This result indicates a sequential order of transcriptional changes in pathways of cell cycle, gene regulation, translation and metabolism, acting in a step-wise fashion from cleavage to morula. Cross-species comparisons with mouse pre-implantation embryos reveal that the majority of human stage-specific modules (7 out of 9) are notably preserved, but developmental specificity and timing differ between human and mouse. Furthermore, we identify conserved key members (or hub genes) of the human and mouse networks. These genes represent novel candidates that are likely to be key in driving mammalian pre-implantation development. Together, the results provide a valuable resource to dissect gene regulatory mechanisms underlying progressive development of early mammalian embryos.