A single-cell molecular map of mouse gastrulation and early organogenesis,Nature

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A single-cell molecular map of mouse gastrulation and early organogenesis
Nature ( IF 50.5 ) Pub Date : 2019-02-01 , DOI: 10.1038/s41586-019-0933-9
Blanca Pijuan-Sala _{1,

2} , Jonathan A Griffiths ₃ , Carolina Guibentif _{1,

2} , Tom W Hiscock _{3,

4} , Wajid Jawaid _{1,

2} , Fernando J Calero-Nieto _{1,

2} , Carla Mulas ₂ , Ximena Ibarra-Soria ₃ , Richard C V Tyser ₅ , Debbie Lee Lian Ho ₂ , Wolf Reik _{6,

7,

8} , Shankar Srinivas ₅ , Benjamin D Simons _{2,

4,

9} , Jennifer Nichols ₂ , John C Marioni _{3,

8,

10} , Berthold Göttgens _{1,

2}

Affiliation

Across the animal kingdom, gastrulation represents a key developmental event during which embryonic pluripotent cells diversify into lineage-specific precursors that will generate the adult organism. Here we report the transcriptional profiles of 116,312 single cells from mouse embryos collected at nine sequential time points ranging from 6.5 to 8.5 days post-fertilization. We construct a molecular map of cellular differentiation from pluripotency towards all major embryonic lineages, and explore the complex events involved in the convergence of visceral and primitive streak-derived endoderm. Furthermore, we use single-cell profiling to show that Tal1−/− chimeric embryos display defects in early mesoderm diversification, and we thus demonstrate how combining temporal and transcriptional information can illuminate gene function. Together, this comprehensive delineation of mammalian cell differentiation trajectories in vivo represents a baseline for understanding the effects of gene mutations during development, as well as a roadmap for the optimization of in vitro differentiation protocols for regenerative medicine.Single-cell profiling is used to create a molecular-level atlas of cell differentiation trajectories during gastrulation and early organogenesis in the mouse.

中文翻译：

小鼠原肠胚形成和早期器官发生的单细胞分子图

在整个动物界，原肠胚形成代表了一个关键的发育事件，在此期间胚胎多能细胞分化为谱系特异性前体细胞，从而产生成年生物体。在这里，我们报告了在受精后 6.5 至 8.5 天的 9 个连续时间点收集的 116,312 个小鼠胚胎单细胞的转录谱。我们构建了从多能性向所有主要胚胎谱系的细胞分化的分子图谱，并探索了内脏和原条衍生内胚层融合所涉及的复杂事件。此外，我们使用单细胞分析来表明 Tal1−/− 嵌合胚胎在早期中胚层多样化中表现出缺陷，因此我们证明了如何结合时间和转录信息来阐明基因功能。总之，这种对哺乳动物细胞体内分化轨迹的全面描述代表了理解发育过程中基因突变影响的基线，以及优化再生医学体外分化方案的路线图。单细胞分析用于创建小鼠原肠胚形成和早期器官发生过程中细胞分化轨迹的分子水平图谱。

更新日期：2019-02-01

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