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

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 mod...

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Main Authors: 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, Naihe Jing
Format: Article
Language:English
Published: Nature Portfolio 2023-09-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-41482-5
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author 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
Naihe Jing
author_facet 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
Naihe Jing
author_sort Ran Wang
collection DOAJ
description 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.
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spelling doaj.art-843d895fd4d14dc49ffa9a2deb1ffa4e2023-11-20T10:00:29ZengNature PortfolioNature Communications2041-17232023-09-0114111810.1038/s41467-023-41482-5Time space and single-cell resolved tissue lineage trajectories and laterality of body plan at gastrulationRan Wang0Xianfa Yang1Jiehui Chen2Lin Zhang3Jonathan A. Griffiths4Guizhong Cui5Yingying Chen6Yun Qian7Guangdun Peng8Jinsong Li9Liantang Wang10John C. Marioni11Patrick P. L. Tam12Naihe Jing13State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of SciencesGuangzhou National LaboratoryState Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of SciencesState Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of SciencesCancer Research UK Cambridge Institute, University of CambridgeGuangzhou National LaboratoryGuangzhou National LaboratoryState Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of SciencesCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesState Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of SciencesSchool of Mathematics, Northwest UniversityCancer Research UK Cambridge Institute, University of CambridgeEmbryology Research Unit, Children’s Medical Research Institute, University of SydneyState Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of SciencesAbstract 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.https://doi.org/10.1038/s41467-023-41482-5
spellingShingle 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
Naihe Jing
Time space and single-cell resolved tissue lineage trajectories and laterality of body plan at gastrulation
Nature Communications
title Time space and single-cell resolved tissue lineage trajectories and laterality of body plan at gastrulation
title_full Time space and single-cell resolved tissue lineage trajectories and laterality of body plan at gastrulation
title_fullStr Time space and single-cell resolved tissue lineage trajectories and laterality of body plan at gastrulation
title_full_unstemmed Time space and single-cell resolved tissue lineage trajectories and laterality of body plan at gastrulation
title_short Time space and single-cell resolved tissue lineage trajectories and laterality of body plan at gastrulation
title_sort time space and single cell resolved tissue lineage trajectories and laterality of body plan at gastrulation
url https://doi.org/10.1038/s41467-023-41482-5
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