中文摘要：

哺乳动物早期胚胎发育过程中,全能的受精卵和早期卵裂球如何打破对称分裂并建立第一次细胞谱系,是发育生物学乃至生命科学研究最具挑战的科学问题之一.为研究哺乳动物第一次细胞谱系建立,早期研究提出过多种理论模型,但都不能很好地解释早期胚胎的可塑性.近年来,随着显微观察、生物数学、以及单细胞测序等技术的发展,人们认识到哺乳动物早期胚胎中,细胞内大分子的表达和分布、细胞的位置和极性,以及细胞间相互作用等多种因素,造成了同一个胚胎中的不同细胞差异显著,即早期胚胎的异质性.哺乳动物早期胚胎的异质性可能是其可塑的主要原因.哺乳动物早期胚胎中不对称分裂的打破和第一次细胞命运决定是一个高度动态和复杂的过程,需要新的技术和理论来阐述这一重要生命现象.

英文摘要：

Mouse pre-implantation embryogenesis is featured by several rounds of sequential cleavages, followed by the first cell lineage formation, specification of the inner cell mass （ICM） and trophectoderm （TE） at blastocyst stage. Establishment of the first cell lineage through asymmetric cell division is a longstanding question in developmental biology. Based on analogy to other lower model organisms or early achievements in mammalian development, three classic models of the first cell lineage specification are proposed to address this question： The prepattem or mosaic model, the inside-outside or positional model, and the polarization model. However, none of these models could well explain the highly regulatory nature of early mammalian embryos. During the past decades, great efforts have been made to elucidate when and how the pre-implantation blastomeres become different and finally segregate from each other. Mounting evidences show that the fate of trophectoderm is regulated by the Hippo/Yap/Tead signaling cascade in mouse early embryogenesis. In addition, single cell profiling and living imaging illustrate the great heterogeneity between blastomeres, providing some explanations for the regulatory nature of mammalian early embryos. Accompanying these progresses, a self-organization model was recently proposed to explain the blastocyst patterning in mammalian early embryos. This new model reconciles the experimental findings that seem to be contradictory to the three classic models and thus is regarded as a reformulation but improvement of classic models. Even so, however, the exact molecular mechanisms underlying this highly dynamic, complex and self-regulative process remain enigmatic. In this review, using mouse as the model system, we firstly summarize the preimplantation development and the classic models of the first cell lineage specification. Then, we highlight recent progresses, especially, the contributions of molecular regulators and heterogeneity of blastomeres in orchestrating the segregation