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哺乳动物器官发生的单细胞转录组图谱。

The single-cell transcriptional landscape of mammalian organogenesis.

机构信息

Department of Genome Sciences, University of Washington, Seattle, WA, USA.

Molecular and Cellular Biology Program, University of Washington, Seattle, WA, USA.

出版信息

Nature. 2019 Feb;566(7745):496-502. doi: 10.1038/s41586-019-0969-x. Epub 2019 Feb 20.


DOI:10.1038/s41586-019-0969-x
PMID:30787437
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6434952/
Abstract

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.

摘要

哺乳动物器官发生是一个显著的过程。在很短的时间内,三个胚层的细胞转化为一个胚胎,其中包括大多数主要的内部和外部器官。在这里,我们以单细胞分辨率研究了小鼠器官发生的转录动态。我们使用单细胞组合索引,在单个实验中对来自 61 个胚胎的约 200 万个细胞的转录组进行了分析,这些胚胎在妊娠 9.5 至 13.5 天之间进行了分期。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发育过程的全局视图。我们使用 Monocle 3 来识别数百种细胞类型和 56 条轨迹,其中许多轨迹仅因为细胞覆盖的深度而被检测到,它们共同定义了数千个相应的标记基因。我们探索了细胞类型和轨迹中随时间表达的动态,包括对顶外胚层脊、肢间充质和骨骼肌的重点分析。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5265/6434952/cffcd220f7c0/nihms-1518381-f0006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5265/6434952/cffcd220f7c0/nihms-1518381-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5265/6434952/d241bed049cc/nihms-1518381-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5265/6434952/5e1e7d75bb77/nihms-1518381-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5265/6434952/91ad8d723fb6/nihms-1518381-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5265/6434952/75b3b45a434c/nihms-1518381-f0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5265/6434952/703d181549ef/nihms-1518381-f0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5265/6434952/17d87ce4195e/nihms-1518381-f0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5265/6434952/b285da17a4f1/nihms-1518381-f0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5265/6434952/b90f8a7f9431/nihms-1518381-f0014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5265/6434952/7129f85713ca/nihms-1518381-f0015.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5265/6434952/5326d1fffb02/nihms-1518381-f0018.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5265/6434952/92f0828f8dd6/nihms-1518381-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5265/6434952/0ccafe9f70f0/nihms-1518381-f0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5265/6434952/cffcd220f7c0/nihms-1518381-f0006.jpg

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本文引用的文献

[1]
Scrublet: Computational Identification of Cell Doublets in Single-Cell Transcriptomic Data.

Cell Syst. 2019-4-3

[2]
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Genome Biol. 2019-3-19

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Science. 2018-8-30

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Cell. 2018-8-9

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Science. 2018-4-26

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