The single-cell transcriptional landscape of mammalian organogenesis
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. Usin...
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Published in | Nature (London) Vol. 566; no. 7745; pp. 496 - 502 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
01.02.2019
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | 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.
Data from single-cell combinatorial-indexing RNA-sequencing analysis of 2 million cells from mouse embryos between embryonic days 9.5 and 13.5 are compiled in a cell atlas of mouse organogenesis, which provides a global view of developmental processes occurring during this critical period. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Equally contributing Author Contributions J.C. developed techniques and performed sci-RNA-seq3 experiments with assistance from M.S., F.Z., L.C., F.S.; M.S. performed embryo collection and in-situ hybridization validations with assistance from D.I. and S.M.; J.C. and C.T. performed computation analysis with assistance from M.S., X.Q. and A.H.; X.Q. and C.T. developed Monocle 3. X.H. developed website with assistance from J.C.; J.S. and C.T. supervised the project; J.S., C.T., J.C. and M.S. conceived the project and wrote the manuscript. Author Information Reprints and permissions information is available at www.nature.com/reprints. L.C., F.Z. and F.S. declare competing financial interests in the form of stock ownership and paid employment by Illumina, Inc. One or more embodiments of one or more patents and patent applications filed by Illumina may encompass the methods, reagents, and data disclosed in this manuscript. Some work in this study may be related to technology described in the following exemplary published patent applications: WO2010/0120098 and WO2011/0287435. Readers are welcome to comment on the online version of the paper. Correspondence and requests for materials should be addressed to J.S. (shendure@uw.edu) or C.T. (coletrap@uw.edu). |
ISSN: | 0028-0836 1476-4687 1476-4687 |
DOI: | 10.1038/s41586-019-0969-x |