Abstract:The progression of the mammalian embryo from fertilization to gastrulation involves an ordered series of hierarchical lineage determination and specifications that ensures the establishment of a blueprint for the whole animal body. For a better understanding of the pluriopotency and the translational application of stem cells， it is crucial to investigate the molecular regulation underlying the sequential lineage specification. This article reviewed the recent progress in our efforts to explore the key regulation of stem cell lineage， especially under the support of “Strategic Priority Research Projecton Stem Cell and Regenerative Medicine” by the Chinese Academy of Sciences.