Morris Samantha A, Zernicka-Goetz Magdalena
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Results Probl Cell Differ. 2012;55:203-17. doi: 10.1007/978-3-642-30406-4_11.
Early development of the mouse comprises a sequence of cell fate decisions in which cells are guided along a pathway of restricted potential and increasing specialisation. The first choice faced by cells of the embryo is whether to become trophectoderm (TE) or inner cell mass (ICM); TE is an extra-embryonic tissue which will form the embryonic portion of the placenta, whilst ICM gives rise to cells responsible for generating the foetus. In the second cell fate decision, the ICM is further refined into pluripotent cells forming the future body of the embryo, epiblast (EPI) and extra-embryonic primitive endoderm (PE), a tissue essential for patterning the embryo and establishing the developmental circulation. Understanding this early lineage segregation is critical for informing attempts to capture pluripotency and direct cell fate in vitro. Unlike the predictability of nonmammalian cell fate, development of the mouse embryo retains the flexibility to adapt to changing circumstances during development. Here we describe these first cell fate decisions, how they can be biased whilst maintaining flexibility and, finally, some of the molecular circuitry underlying early fate choice.
小鼠的早期发育包含一系列细胞命运决定,在此过程中,细胞沿着潜能受限且特化程度不断提高的途径发展。胚胎细胞面临的第一个选择是成为滋养外胚层(TE)还是内细胞团(ICM);TE是一种胚外组织,将形成胎盘的胚胎部分,而ICM产生的细胞则负责生成胎儿。在第二个细胞命运决定中,ICM进一步分化为形成胚胎未来主体的多能细胞、上胚层(EPI)和胚外原始内胚层(PE),PE是一种对胚胎模式形成和建立发育循环至关重要的组织。了解这种早期谱系分离对于指导在体外捕获多能性和定向细胞命运的尝试至关重要。与非哺乳动物细胞命运的可预测性不同,小鼠胚胎的发育在发育过程中保留了适应变化环境的灵活性。在这里,我们描述了这些最初的细胞命运决定、它们在保持灵活性的同时如何产生偏差,以及最后,早期命运选择背后的一些分子机制。