Biase et al

在哺乳动物中何时以及如何做出第一个细胞命运决定仍然是一个悬而未决的问题。使用匹配的姐妹卵裂球的深度单细胞 RNA-seq，我们报告了 10 个 2 细胞和 5 个 4 细胞小鼠胚胎之间高度可重复的卵裂球间差异。卵裂球间基因表达差异主导胚胎间差异和噪音，并且足以将姐妹卵裂球聚集成不同的组。数十个蛋白质编码基因在姐妹卵裂球中表现出可重复的双峰表达（FPKM 的 0 对 1e3-1e6），这不能用随机波动来解释。这些双峰基因之一 Gadd45a 的蛋白质表达表现出明显的卵裂粒间对比。我们将一些双峰 mRNA 表达追踪到胚胎基因组激活，而另一些则追踪到卵裂球特异性 RNA 消耗。卵裂球间的差异产生了比随机噪声可能产生的更强大和更大的共表达基因网络。 4 细胞中高度相关的基因对与显示内细胞团 (ICM) 和滋养外胚层 (TE) 之间差异表达方向相同的基因对重叠。这些数据证实了 2 细胞和 4 细胞小鼠胚胎中卵裂球间差异的假设，并将这些差异与 ICM/TE 差异相关联。

When and how the first cell fate decision is made in mammals remains an open question. Using deep single-cell RNA-seq on matched sister blastomeres, we report highly reproducible inter-blastomere differences between 10 2-cell and 5 4-cell mouse embryos. Inter-blastomere gene expression differences dominate inter-embryo differences and noise, and are sufficient to cluster sister blastomeres into distinct groups. Dozens of protein-coding genes exhibit reproducible bimodal expression in sister blastomeres (0 vs 1e3–1e6 in FPKM), which cannot be explained by stochastic fluctuations. Protein expression of Gadd45a, one of these bimodal genes, displays distinct inter-blastomere differences. We trace some of these bimodal mRNA expressions to embryonic genome activation, while others to blastomere-specific RNA degradation. Inter-blastomere differences give rise to co-expressed gene networks that are more robust and larger than those potentially generated by random noise. Highly correlated gene pairs in 4-cell embryos overlap with those that exhibit the same direction of differential expression between the inner cell mass (ICM) and trophectoderm (TE). These data confirm the hypothesis of inter-blastomere differences in 2-cell and 4-cell mouse embryos, and associate these differences with the ICM/TE differences.

搜集汇总

背景与挑战

背景概述

该数据集源自一项2014年的研究，通过单细胞RNA测序技术分析了小鼠早期胚胎（2细胞和4细胞阶段）的卵裂球。研究发现卵裂球间存在显著的基因表达差异，其中数十个基因呈现双峰表达模式，这些差异与后续内细胞团和滋养外胚层的分化方向相关联。