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. single-cell RNA-seq of monkey, human, and mouse embryos Please note that the raw data for GSM1977282 is not provided.哺乳动物着床前发育在不同物种间存在高度保守的遗传程序，但不同物种间亦存在基因网络激活的时序差异与基因模块的成员组成差异。本研究以人类、猴类及小鼠为模型，旨在解析不同物种中滋养外胚层（trophoectoderm, TE）与内细胞团（inner cell mass, ICM）内关键基因网络的激活模式。通过对食蟹猴早期胚胎开展单细胞RNA测序分析，我们发现其主要胚胎基因组激活（embryonic genome activation, EGA）发生于早期桑椹胚阶段，时序相对滞后。基因网络保守性分析结果显示，相较于小鼠，猴类胚胎的遗传程序与人类胚胎更为相似，这佐证了灵长类着床前发育与啮齿类存在分化的观点。例如，灵长类囊胚的内细胞团与滋养外胚层相关基因呈现差异化表达（如X、Y基因），而小鼠的此类表达差异则体现于A、B基因。值得关注的是，在三个研究物种中，滋养外胚层基因网络的整体保守性均高于内细胞团，这提示滋养外胚层谱系分化的发育程序更为保守。此外，滋养外胚层特异性基因网络仅在囊胚阶段激活，在桑椹胚或更早的胚胎中表达量极低或无表达。与之相对，大多数内细胞团特异性基因在首次主要胚胎基因组激活（EGA）浪潮中即被强力激活，并在晚期桑椹胚与囊胚阶段得到进一步精细化调控。综上，本研究为哺乳动物着床前发育以及滋养外胚层与内细胞团谱系特异性遗传程序的时序激活提供了全新的研究视角。本数据集涵盖猴、人类及小鼠胚胎的单细胞RNA测序数据。请注意，GSM1977282的原始数据未提供。