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A spatially resolved single cell atlas of human gastrulation

Richard C.V. Tyser, Elmir Mahammadov, Shota Nakanoh, View ORCID ProfileLudovic Vallier, Antonio Scialdone, View ORCID ProfileShankar Srinivas
doi: https://doi.org/10.1101/2020.07.21.213512
Richard C.V. Tyser
1Department of Physiology, Anatomy and Genetics, South Parks Road, University of Oxford, Oxford, OX1 3QX, UK
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Elmir Mahammadov
2Institute of Epigenetics and Stem Cells, Helmholtz Zentrum München – German Research Center for Environmental Health, Munich, 81377, Germany
3Institute of Functional Epigenetics, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, 85764, Germany
4Institute of Computational Biology, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, 85764, Germany
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Shota Nakanoh
5Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge Biomedical Campus, Cambridge, CB2 0AW, UK
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Ludovic Vallier
5Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge Biomedical Campus, Cambridge, CB2 0AW, UK
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  • ORCID record for Ludovic Vallier
Antonio Scialdone
2Institute of Epigenetics and Stem Cells, Helmholtz Zentrum München – German Research Center for Environmental Health, Munich, 81377, Germany
3Institute of Functional Epigenetics, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, 85764, Germany
4Institute of Computational Biology, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, 85764, Germany
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  • For correspondence: antonio.scialdone@helmholtz-muenchen.de shankar.srinivas@dpag.ox.ac.uk
Shankar Srinivas
1Department of Physiology, Anatomy and Genetics, South Parks Road, University of Oxford, Oxford, OX1 3QX, UK
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  • ORCID record for Shankar Srinivas
  • For correspondence: antonio.scialdone@helmholtz-muenchen.de shankar.srinivas@dpag.ox.ac.uk
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ABSTRACT

Gastrulation is the fundamental process during the embryogenesis of all multicellular animals through which the basic body plan is first laid down. It is pivotal in generating cellular diversity coordinated with spatial patterning. Gastrulation in humans occurs in the third week following fertilization. Our understanding of this process in humans is extremely limited, and based almost entirely on experimental models. Here, we characterize in a spatially resolved manner the single cell transcriptional profile of an entire gastrulating human embryo approximately 16 to 19 days after fertilization. We used these data to provide the first unequivocal demonstration that human embryonic stem cells represent the early post implantation epiblast. We identified both primordial germ cells and red blood cells, which had never been characterized so early during human development. Comparison with mouse gastrula transcriptomes revealed many commonalities between the human and mouse but also several key differences, particularly in FGF signaling, that we validated experimentally. This unique dataset offers a unique glimpse into a central but generally inaccessible stage of our development, provides new context for interpreting experiments in other model systems and represents a valuable resource for guiding directed differentiation of human cells in vitro.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵6 These authors jointly supervised this work

  • http://www.human-gastrula.net

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 21, 2020.
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A spatially resolved single cell atlas of human gastrulation
Richard C.V. Tyser, Elmir Mahammadov, Shota Nakanoh, Ludovic Vallier, Antonio Scialdone, Shankar Srinivas
bioRxiv 2020.07.21.213512; doi: https://doi.org/10.1101/2020.07.21.213512
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A spatially resolved single cell atlas of human gastrulation
Richard C.V. Tyser, Elmir Mahammadov, Shota Nakanoh, Ludovic Vallier, Antonio Scialdone, Shankar Srinivas
bioRxiv 2020.07.21.213512; doi: https://doi.org/10.1101/2020.07.21.213512

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