PDF(Pubmed)
Abstract：
Cell-fate decisions during mammalian gastrulation are poorly understood outside of rodent embryos. The embryonic disc of pig embryos mirrors humans, making them a useful proxy for studying gastrulation. Here we present a single-cell transcriptomic atlas of pig gastrulation, revealing cell-fate emergence dynamics, as well as conserved and divergent gene programs governing early porcine, primate, and murine development. We highlight heterochronicity in extraembryonic cell-types, despite the broad conservation of cell-type-specific transcriptional programs. We apply these findings in combination with functional investigations, to outline conserved spatial, molecular, and temporal events during definitive endoderm specification. We find early FOXA2 + /TBXT- embryonic disc cells directly form definitive endoderm, contrasting later-emerging FOXA2/TBXT+ node/notochord progenitors. Unlike mesoderm, none of these progenitors undergo epithelial-to-mesenchymal transition. Endoderm/Node fate hinges on balanced WNT and hypoblast-derived NODAL, which is extinguished upon endodermal differentiation. These findings emphasise the interplay between temporal and topological signalling in fate determination during gastrulation.
摘要：
在啮齿动物胚胎之外，对哺乳动物原肠胚形成过程中的细胞命运决定知之甚少。猪胚胎的胚胎盘反映了人类，使它们成为研究胃肠病的有用代理。在这里，我们提出了猪原肠胚形成的单细胞转录组学图谱，揭示细胞命运出现的动态，以及管理早期猪的保守和不同的基因程序，灵长类动物,和鼠的发展。我们强调胚胎外细胞类型的异时间性，尽管细胞类型特异性转录程序广泛保守。我们将这些发现与功能调查相结合，勾勒出保守的空间，分子，确定内胚层规范期间的时间事件。我们发现早期FOXA2+/TBXT-胚胎椎间盘细胞直接形成定形内胚层，对比后来出现的FOXA2/TBXT+节点/脊索祖细胞。不像中胚层,这些祖细胞都没有经历上皮-间质转化。内胚层/节点的命运取决于平衡的WNT和下爆炸来源的NODAL，在内胚层分化后消失。这些发现强调了原肠胚形成过程中命运决定中时间和拓扑信号之间的相互作用。
