Athanasouli Paraskevi, Vanhessche Tijs, Lluis Frederic
Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium
Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium.
Life Sci Alliance. 2025 Jan 8;8(3). doi: 10.26508/lsa.202403091. Print 2025 Mar.
Mammalian pre-implantation development is entirely devoted to the specification of extra-embryonic lineages, which are fundamental for embryo morphogenesis and support. The second fate decision is taken just before implantation, as defined by the epiblast (EPI) and the primitive endoderm (PE) specification. Later, EPI forms the embryo proper and PE contributes to the formation of the yolk sac. The formation of EPI and PE as molecularly and morphologically distinct lineages is the final step of a multistage process, which begins when bipotent progenitor cells diverge into separate fates. Despite advances in uncovering the molecular mechanisms underlying the differential transcriptional patterns that dictate how apparently identical cells make fate decisions and how lineage integrity is maintained, a detailed overview of these mechanisms is still lacking. In this review, we dissect the EPI and PE formation process into four stages (initiation, specification, segregation, and maintenance) and we provide a comprehensive understanding of the molecular mechanisms involved in lineage establishment in the mouse. In addition, we discuss the conservation of key processes in humans, based on the most recent findings.
哺乳动物植入前发育完全致力于胚外谱系的特化，这对胚胎形态发生和支持至关重要。第二次命运决定恰好在植入前做出，由上胚层（EPI）和原始内胚层（PE）的特化所定义。随后，EPI形成胚胎本体，PE则有助于卵黄囊的形成。EPI和PE作为分子和形态上不同的谱系的形成是一个多阶段过程的最后一步，该过程始于双能祖细胞分化为不同的命运。尽管在揭示决定看似相同的细胞如何做出命运决定以及如何维持谱系完整性的差异转录模式背后的分子机制方面取得了进展，但仍缺乏对这些机制的详细概述。在本综述中，我们将EPI和PE的形成过程分为四个阶段（起始、特化、分离和维持），并对小鼠谱系建立过程中涉及的分子机制提供全面的理解。此外，我们根据最新研究结果讨论了人类关键过程的保守性。
