Developmental Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Genome Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Nat Cell Biol. 2014 Jan;16(1):27-37. doi: 10.1038/ncb2881. Epub 2013 Dec 1.
It is now recognized that extensive expression heterogeneities among cells precede the emergence of lineages in the early mammalian embryo. To establish a map of pluripotent epiblast (EPI) versus primitive endoderm (PrE) lineage segregation within the inner cell mass (ICM) of the mouse blastocyst, we characterized the gene expression profiles of individual ICM cells. Clustering analysis of the transcriptomes of 66 cells demonstrated that initially they are non-distinguishable. Early in the segregation, lineage-specific marker expression exhibited no apparent correlation, and a hierarchical relationship was established only in the late blastocyst. Fgf4 exhibited a bimodal expression at the earliest stage analysed, and in its absence, the differentiation of PrE and EPI was halted, indicating that Fgf4 drives, and is required for, ICM lineage segregation. These data lead us to propose a model where stochastic cell-to-cell expression heterogeneity followed by signal reinforcement underlies ICM lineage segregation by antagonistically separating equivalent cells.
现在人们已经认识到，在早期哺乳动物胚胎中谱系出现之前，细胞之间就存在广泛的表达异质性。为了在小鼠囊胚的内细胞团 (ICM) 中建立多能上胚层 (EPI) 与原始内胚层 (PrE) 谱系分离的图谱，我们对单个 ICM 细胞的基因表达谱进行了描述。对 66 个细胞的转录组进行聚类分析表明，它们最初是不可区分的。在早期的分离过程中，谱系特异性标记的表达没有明显的相关性，只有在晚期囊胚中才建立了层次关系。在分析的最早阶段，Fgf4 表现出双峰表达，而在没有 Fgf4 的情况下，PrE 和 EPI 的分化停止，这表明 Fgf4 驱动并需要 ICM 谱系分离。这些数据使我们提出了一个模型，即在信号增强之前，细胞间随机的表达异质性导致了 ICM 谱系的分离，从而将等效细胞拮抗地分离。
