Abstract:
The hourglass model describes the convergence of species within the same phylum to a similar body plan during development; however, the molecular mechanisms underlying this phenomenon in mammals remain poorly described. Here, we compare rabbit and mouse time-resolved differentiation trajectories to revisit this model at single-cell resolution. We modeled gastrulation dynamics using hundreds of embryos sampled between gestation days 6.0 and 8.5 and compared the species using a framework for time-resolved single-cell differentiation-flows analysis. We find convergence toward similar cell-state compositions at E7.5, supported by the quantitatively conserved expression of 76 transcription factors, despite divergence in surrounding trophoblast and hypoblast signaling. However, we observed noticeable changes in specification timing of some lineages and divergence of primordial germ cell programs, which in the rabbit do not activate mesoderm genes. Comparative analysis of temporal differentiation models provides a basis for studying the evolution of gastrulation dynamics across mammals.
摘要:
沙漏模型描述了同一门内的物种在开发过程中收敛到类似的身体计划;但是,哺乳动物中这种现象背后的分子机制仍然缺乏描述。这里,我们比较了兔和小鼠的时间分辨分化轨迹,以单细胞分辨率重新评估该模型.我们使用在妊娠第6.0天和第8.5天之间采样的数百个胚胎对原肠胚动力学进行了建模,并使用时间分辨的单细胞分化流分析框架比较了该物种。我们发现E7.5的细胞状态组成趋同,由76个转录因子的定量保守表达支持,尽管周围的滋养层和下胚层信号存在差异。然而,我们观察到一些谱系的规格时间和原始生殖细胞程序的分歧发生了明显的变化,在兔子中不激活中胚层基因。时间分化模型的比较分析为研究哺乳动物的原肠胚形成动力学的演变提供了基础。