Single-cell analysis of gene networks in trophoectoderm and inner cell mass during human, monkey and mouse preimplantation development

Mammalian preimplantation development involves highly conserved genetic programs across species. However, temporal differences in gene network activation and membership differences in gene modules are also observed. In this study, we focus on understanding the activation of crucial gene networks in trophoectoderm (TE) and inner cell mass across species using human, monkey, and mouse models. By single cell RNA sequencing analysis in cynomolgus monkey early embryos, we find relatively late major embryonic genome activation occurring at early morula stages. Gene network preservation analysis reveals that genetic programs in monkey embryos more closely resemble human embryos compared to mouse, supporting the notion that preimplantation development in primate species are divergent from rodent species. For example, primate blastocysts show differential expression of ICM and TE genes such as X and Y, whereas mouse show differences in A and B expression. Interestingly, the overall conservation of TE gene networks is higher than ICM across three species, suggesting a more conserved developmental program in TE lineage differentiation. Additionally, TE-specific gene networks are exclusively activated at the blastocyst stage with low or no expression in morula or earlier embryos. In contrast, a majority of ICM-specific genes are strongly activated during the first major wave of EGA, which are further fine-tuned during late morula and blastocyst stages. Taken together, our study provides new insight into mammalian preimplantation development and sequential activation of lineage-specific genetic programs of TE versus ICM. Overall design: single-cell RNA-seq of monkey, human, and mouse embryos Please note that the raw data for GSM1977282 is not provided.