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Time space and single-cell resolved tissue lineage trajectories and laterality of body plan at gastrulation

Ran Wang, Xianfa Yang, Jiehui Chen, Lin Zhang, Jonathan A. Griffiths, Guizhong Cui, Yingying Chen, Yun Qian, Guangdun Peng, Jinsong Li, Liantang Wang, John C. Marioni, Patrick P. L. Tam () and Naihe Jing ()
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Ran Wang: CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences
Xianfa Yang: Guangzhou National Laboratory
Jiehui Chen: CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences
Lin Zhang: CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences
Jonathan A. Griffiths: University of Cambridge
Guizhong Cui: Guangzhou National Laboratory
Yingying Chen: Guangzhou National Laboratory
Yun Qian: CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences
Guangdun Peng: Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
Jinsong Li: CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences
Liantang Wang: Northwest University
John C. Marioni: University of Cambridge
Patrick P. L. Tam: University of Sydney
Naihe Jing: CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Understanding of the molecular drivers of lineage diversification and tissue patterning during primary germ layer development requires in-depth knowledge of the dynamic molecular trajectories of cell lineages across a series of developmental stages of gastrulation. Through computational modeling, we constructed at single-cell resolution, a spatio-temporal transcriptome of cell populations in the germ-layers of gastrula-stage mouse embryos. This molecular atlas enables the inference of molecular network activity underpinning the specification and differentiation of the germ-layer tissue lineages. Heterogeneity analysis of cellular composition at defined positions in the epiblast revealed progressive diversification of cell types. The single-cell transcriptome revealed an enhanced BMP signaling activity in the right-side mesoderm of late-gastrulation embryo. Perturbation of asymmetric BMP signaling activity at late gastrulation led to randomization of left-right molecular asymmetry in the lateral mesoderm of early-somite-stage embryo. These findings indicate the asymmetric BMP activity during gastrulation may be critical for the symmetry breaking process.

Date: 2023
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DOI: 10.1038/s41467-023-41482-5

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