State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun-Ye-Sat University, Guangzhou, China.
Department of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
Dev Dyn. 2021 Jul;250(7):974-985. doi: 10.1002/dvdy.295. Epub 2021 Feb 4.
Genetic programs underlying preimplantation development and early lineage segregation are highly conserved across mammals. It has been suggested that nonhuman primates would be better model organisms for human embryogenesis, but a limited number of studies have investigated the monkey preimplantation development. In this study, we collect single cells from cynomolgus monkey preimplantation embryos for transcriptome profiling and compare with single-cell RNA-seq data derived from human and mouse embryos.
By weighted gene-coexpression network analysis, we found that cynomolgus gene networks have greater conservation with human embryos including a greater number of conserved hub genes than that of mouse embryos. Consistently, we found that early ICM/TE lineage-segregating genes in monkeys exhibit greater similarity with human when compared to mouse, so are the genes in signaling pathways such as LRP1 and TCF7 involving in WNT pathway. Last, we tested the role of one conserved pre-EGA hub gene, SIN3A, using a morpholino knockdown of maternal RNA transcripts in monkey embryos followed by single-cell RNA-seq. We found that SIN3A knockdown disrupts the gene-silencing program during the embryonic genome activation transition and results in developmental delay of cynomolgus embryos.
Taken together, our study provided new insight into evolutionarily conserved and divergent transcriptome dynamics during mammalian preimplantation development.
在哺乳动物中，胚胎植入前发育和早期谱系分离的遗传程序高度保守。人们曾认为非人类灵长类动物将是研究人类胚胎发生的更好的模式生物，但仅有少数研究调查了猴子的胚胎植入前发育。在这项研究中，我们从食蟹猴胚胎中收集单细胞进行转录组谱分析，并与源自人类和小鼠胚胎的单细胞 RNA-seq 数据进行比较。
通过加权基因共表达网络分析，我们发现食蟹猴基因网络与人类胚胎的保守性更大，包括比小鼠胚胎更多的保守枢纽基因。一致地，我们发现猴子中早期 ICM/TE 谱系分离基因与人类的相似性更大，而与小鼠的相似性更小，参与 WNT 通路的 LRP1 和 TCF7 等信号通路基因也是如此。最后，我们使用食蟹猴胚胎中的母体 RNA 转录本的 morpholino 敲低来测试一个保守的 EGA 枢纽基因 SIN3A 的作用，随后进行单细胞 RNA-seq。我们发现 SIN3A 敲低破坏了胚胎基因组激活过渡期间的基因沉默程序，并导致食蟹猴胚胎发育延迟。
总之，我们的研究为哺乳动物胚胎植入前发育过程中进化保守和分化的转录组动态提供了新的见解。
