Toyooka Yayoi
Center for iPS Cell Research and Application (CiRA) Kyoto University Kyoto Japan.
Reprod Med Biol. 2020 Jul 2;19(3):209-221. doi: 10.1002/rmb2.12333. eCollection 2020 Jul.
The establishment of the trophectoderm (TE) and the inner cell mass (ICM) is the first cell lineage segregation that occurs in mammalian preimplantation development. TE will contribute to the placenta while ICM cells give rise to the epiblast (EPI) and primitive endoderm (PrE). There are two historical models for TE/ICM segregation: the positional (inside-outside) model and the polarity model, but both models alone cannot explain the mechanism of TE/ICM segregation.
This article discusses a current possible model based on recent studies including the finding through live-cell imaging of the expression patterns of caudal type homeobox 2 (Cdx2), a key transcription factor of TE differentiation in the mouse embryo.
It was observed that a part of outer Cdx2-expressing blastomeres was internalized at the around 20- to 30-cell stage, downregulates Cdx2, ceases TE differentiation, and participates in ICM lineages.
The early blastomere, which starts differentiation toward the TE cell fate, still has plasticity and can change its fate. Differentiation potency of all blastomeres until approximately the 32-cell stage is presumably not irreversibly restricted even if they show heterogeneity in their epigenetic modifications or gene expression patterns.
滋养外胚层(TE)和内细胞团(ICM)的建立是哺乳动物植入前发育过程中发生的首次细胞谱系分离。TE将发育成胎盘,而ICM细胞则产生上胚层(EPI)和原始内胚层(PrE)。关于TE/ICM分离有两种传统模型:位置(由内而外)模型和极性模型,但仅这两种模型都无法解释TE/ICM分离的机制。
本文基于近期研究讨论了一种当前可能的模型,包括通过活细胞成像对小鼠胚胎中TE分化的关键转录因子尾型同源框2(Cdx2)表达模式的研究发现。
观察到一部分表达Cdx2的外层卵裂球在20至30细胞阶段左右内化,下调Cdx2,停止TE分化,并参与ICM谱系的形成。
早期开始向TE细胞命运分化的卵裂球仍具有可塑性,能够改变其命运。即使所有卵裂球在表观遗传修饰或基因表达模式上表现出异质性,直到大约32细胞阶段它们的分化潜能可能也并非不可逆转地受到限制。