The single-cell transcriptional landscape of mammalian organogenesis
The single-cell transcriptional landscape of mammalian organogenesis
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DOI：
10.1038/s41586-019-0969-x
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发表时间：
2019-02-28
期刊：
影响因子：
64.8
通讯作者：
Shendure, Jay
中科院分区：
文献类型：
--
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
哺乳动物的器官发生是一个了不起的过程。在很短的时间内，三个胚层的细胞就会转变成一个胚胎，其中包括大部分主要的内部和外部器官。在这里，我们研究了单细胞分辨率下小鼠器官发生的转录动力学。使用单细胞组合索引，我们在一次实验中描绘了来自61个胚胎的大约200万个细胞的转录本，这些胚胎在怀孕9.5天到13.5天之间。由此产生的《小鼠器官发生细胞图谱》(MOCA)提供了这一关键窗口期间发育过程的全球视角。我们使用Monocle 3来识别数百种细胞类型和56条轨迹，其中许多只是因为细胞覆盖的深度而被检测到，并共同定义了数千个相应的标记基因。我们探索了随着时间的推移，细胞类型和轨迹中基因表达的动态，包括对顶端外胚层脊、肢体间充质和骨骼肌的重点分析。
Mammalian organogenesis is a remarkable process. Within a short timeframe, the cells of the three germ layers transform into an embryo that includes most of the major internal and external organs. Here we investigate the transcriptional dynamics of mouse organogenesis at single-cell resolution. Using single-cell combinatorial indexing, we profiled the transcriptomes of around 2 million cells derived from 61 embryos staged between 9.5 and 13.5 days of gestation, in a single experiment. The resulting 'mouse organogenesis cell atlas' (MOCA) provides a global view of developmental processes during this critical window. We use Monocle 3 to identify hundreds of cell types and 56 trajectories, many of which are detected only because of the depth of cellular coverage, and collectively define thousands of corresponding marker genes. We explore the dynamics of gene expression within cell types and trajectories over time, including focused analyses of the apical ectodermal ridge, limb mesenchyme and skeletal muscle.