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Nature. 2019 Aug;572(7770):528-532. doi: 10.1038/s41586-019-1469-8. Epub 2019 Aug 7.

Molecular architecture of lineage allocation and tissue organization in early mouse embryo.

Peng G1,2,3,4, Suo S5,6, Cui G7, Yu F7, Wang R7, Chen J7, Chen S7, Liu Z7, Chen G5, Qian Y7, Tam PPL8,9, Han JJ10,11, Jing N12,13,14.

Author information

1
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China. peng_guangdun@gibh.ac.cn.
2
CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. peng_guangdun@gibh.ac.cn.
3
Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), Guangzhou, China. peng_guangdun@gibh.ac.cn.
4
Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. peng_guangdun@gibh.ac.cn.
5
CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
6
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, MA, USA.
7
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
8
Embryology Unit, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, Australia.
9
School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Westmead, New South Wales, Australia.
10
CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. jackie.han@pku.edu.cn.
11
Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology (CQB), Peking University, Beijing, China. jackie.han@pku.edu.cn.
12
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China. njing@sibcb.ac.cn.
13
Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. njing@sibcb.ac.cn.
14
School of Life Science and Technology, ShanghaiTech University, Shanghai, China. njing@sibcb.ac.cn.

Abstract

During post-implantation development of the mouse embryo, descendants of the inner cell mass in the early epiblast transit from the naive to primed pluripotent state1. Concurrently, germ layers are formed and cell lineages are specified, leading to the establishment of the blueprint for embryogenesis. Fate-mapping and lineage-analysis studies have revealed that cells in different regions of the germ layers acquire location-specific cell fates during gastrulation2-5. The regionalization of cell fates preceding the formation of the basic body plan-the mechanisms of which are instrumental for understanding embryonic programming and stem-cell-based translational study-is conserved in vertebrate embryos6-8. However, a genome-wide molecular annotation of lineage segregation and tissue architecture of the post-implantation embryo has yet to be undertaken. Here we report a spatially resolved transcriptome of cell populations at defined positions in the germ layers during development from pre- to late-gastrulation stages. This spatiotemporal transcriptome provides high-resolution digitized in situ gene-expression profiles, reveals the molecular genealogy of tissue lineages and defines the continuum of pluripotency states in time and space. The transcriptome further identifies the networks of molecular determinants that drive lineage specification and tissue patterning, supports a role of Hippo-Yap signalling in germ-layer development and reveals the contribution of visceral endoderm to the endoderm in the early mouse embryo.

PMID:
31391582
DOI:
10.1038/s41586-019-1469-8

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