Human axial progenitors generate trunk neural crest cells in vitro

  1. Thomas J R Frith
  2. Ilaria Granata
  3. Matthew Wind
  4. Erin Stout
  5. Oliver Thompson
  6. Katrin Neumann
  7. Dylan Stavish
  8. Paul R Heath
  9. Daniel Ortmann
  10. James O S Hackland
  11. Konstantinos Anastassiadis
  12. Mina Gouti
  13. James Briscoe
  14. Valerie Wilson
  15. Stuart L Johnson
  16. Marysia Placzek
  17. Mario R Guarracino
  18. Peter W Andrews
  19. Anestis Tsakiridis  Is a corresponding author
  1. University of Sheffield, United Kingdom
  2. High Performance Computing and Networking Institute (ICAR), National Research Council of Italy (CNR), Italy
  3. Technische Universität Dresden, Germany
  4. University of Cambridge, United Kingdom
  5. Max Delbrück Center for Molecular Medicine, Germany
  6. The Francis Crick Institute, United Kingdom
  7. University of Edinburgh, United Kingdom

Abstract

The neural crest (NC) is a multipotent embryonic cell population that generates distinct cell types in an axial position-dependent manner. The production of NC cells from human pluripotent stem cells (hPSCs) is a valuable approach to study human NC biology. However, the origin of human trunk NC remains undefined and current in vitro differentiation strategies induce only a modest yield of trunk NC cells. Here we show that hPSC-derived axial progenitors, the posteriorly-located drivers of embryonic axis elongation, give rise to trunk NC cells and their derivatives. Moreover, we define the molecular signatures associated with the emergence of human NC cells of distinct axial identities in vitro. Collectively, our findings indicate that there are two routes toward a human post-cranial NC state: the birth of cardiac and vagal NC is facilitated by retinoic acid-induced posteriorisation of an anterior precursor whereas trunk NC arises within a pool of posterior axial progenitors.

Data availability

The microarray and RNAseq data have been deposited to GEO (GSE109267 and GSE110608).

The following data sets were generated

Article and author information

Author details

  1. Thomas J R Frith

    Centre for Stem Cell Biology, Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6078-5466
  2. Ilaria Granata

    Computational and Data Science Laboratory (CDS-LAB), High Performance Computing and Networking Institute (ICAR), National Research Council of Italy (CNR), Napoli, Italy
    Competing interests
    The authors declare that no competing interests exist.
  3. Matthew Wind

    Centre for Stem Cell Biology, Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Erin Stout

    Centre for Stem Cell Biology, Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Oliver Thompson

    Centre for Stem Cell Biology, Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Katrin Neumann

    Stem Cell Engineering, Biotechnology Center, Technische Universität Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Dylan Stavish

    Centre for Stem Cell Biology, Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Paul R Heath

    Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Daniel Ortmann

    Anne McLaren Laboratory, Wellcome Trust-MRC Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. James O S Hackland

    Centre for Stem Cell Biology, Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7087-9995
  11. Konstantinos Anastassiadis

    Stem Cell Engineering, Biotechnology Center, Technische Universität Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9814-0559
  12. Mina Gouti

    Max Delbrück Center for Molecular Medicine, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  13. James Briscoe

    Developmental Dynamics Lab, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1020-5240
  14. Valerie Wilson

    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4182-5159
  15. Stuart L Johnson

    Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  16. Marysia Placzek

    Department of Biomedical Science, University of Sheffield, Sheffied, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  17. Mario R Guarracino

    Computational and Data Science Laboratory (CDS-LAB), High Performance Computing and Networking Institute (ICAR), National Research Council of Italy (CNR), Napoli, Italy
    Competing interests
    The authors declare that no competing interests exist.
  18. Peter W Andrews

    Centre for Stem Cell Biology, Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  19. Anestis Tsakiridis

    Centre for Stem Cell Biology, Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom
    For correspondence
    a.tsakiridis@sheffield.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2184-2990

Funding

Biotechnology and Biological Sciences Research Council (BB/P000444/1)

  • Mina Gouti
  • Anestis Tsakiridis

Medical Research Council (Mr/K011200/1)

  • James Briscoe
  • Valerie Wilson

Royal Society (RG160249)

  • Anestis Tsakiridis

Cancer Research UK (FC001051)

  • James Briscoe

Wellcome (FC001051)

  • James Briscoe

Seventh Framework Programme (Plurimes)

  • Konstantinos Anastassiadis
  • Peter W Andrews

Royal Society

  • Stuart L Johnson

Biotechnology and Biological Sciences Research Council (BB/J015539/1)

  • Mina Gouti
  • Anestis Tsakiridis

Medical Research Council (FC001051)

  • James Briscoe
  • Valerie Wilson

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Richard M White, Memorial Sloan Kettering Cancer Center, United States

Publication history

  1. Received: February 8, 2018
  2. Accepted: August 9, 2018
  3. Accepted Manuscript published: August 10, 2018 (version 1)
  4. Version of Record published: August 20, 2018 (version 2)

Copyright

© 2018, Frith et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Thomas J R Frith
  2. Ilaria Granata
  3. Matthew Wind
  4. Erin Stout
  5. Oliver Thompson
  6. Katrin Neumann
  7. Dylan Stavish
  8. Paul R Heath
  9. Daniel Ortmann
  10. James O S Hackland
  11. Konstantinos Anastassiadis
  12. Mina Gouti
  13. James Briscoe
  14. Valerie Wilson
  15. Stuart L Johnson
  16. Marysia Placzek
  17. Mario R Guarracino
  18. Peter W Andrews
  19. Anestis Tsakiridis
(2018)
Human axial progenitors generate trunk neural crest cells in vitro
eLife 7:e35786.
https://doi.org/10.7554/eLife.35786

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