Reconstructing human pancreatic differentiation by mapping specific cell populations during development

  1. Cyrille Ramond
  2. Nicolas Glaser
  3. Claire Berthault
  4. Jacqueline Ameri
  5. Jeannette Schlichting Kirkegaard
  6. Mattias Hansson
  7. Christian Honoré
  8. Henrik Semb
  9. Raphaël Scharfmann  Is a corresponding author
  1. Cochin Institute, France
  2. Faculty of Health Sciences, University of Copenhagen, Denmark
  3. Novo Nordisk A/S, Denmark

Abstract

Information remains scarce on human development compared to animal models. Here, we reconstructed human fetal pancreatic differentiation using cell surface markers. We demonstrate that at 7 weeks of development, the glycoprotein 2 (GP2) marks a multipotent cell population that will differentiate into the acinar, ductal or endocrine lineages. Development towards the acinar lineage is paralleled by an increase in GP2 expression. Conversely, a subset of the GP2+ population undergoes endocrine differentiation by down-regulating GP2 and CD142 and turning on NEUROG3, a marker of endocrine differentiation. Endocrine maturation progresses by up-regulating SUSD2 and lowering ECAD levels. Finally, in vitro differentiation of pancreatic endocrine cells derived from human pluripotent stem cells mimics key in vivo events. Our work paves the way to extend our understanding of the origin of mature human pancreatic cell types and how such lineage decisions are regulated.

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The following data sets were generated

Article and author information

Author details

  1. Cyrille Ramond

    INSERM U1016, Cochin Institute, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Nicolas Glaser

    INSERM U1016, Cochin Institute, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Claire Berthault

    INSERM U1016, Cochin Institute, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Jacqueline Ameri

    The Danish Stem Cell Center (DanStem), Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  5. Jeannette Schlichting Kirkegaard

    Department of Islet and Stem Cell Biology, Novo Nordisk A/S, Måløv, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  6. Mattias Hansson

    Global Research External Affairs, Novo Nordisk A/S, Måløv, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  7. Christian Honoré

    Department of Islet and Stem Cell Biology, Novo Nordisk A/S, Måløv, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  8. Henrik Semb

    The Danish Stem Cell Center (DanStem), Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  9. Raphaël Scharfmann

    INSERM U1016, Cochin Institute, Paris, France
    For correspondence
    raphael.scharfmann@inserm.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7619-337X

Funding

European commition's seventh framework program (602587)

  • Raphaël Scharfmann

Innovative medicines initiative (115439)

  • Raphaël Scharfmann

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

Reviewing Editor

  1. Neil A Hanley, University of Manchester, United Kingdom

Publication history

  1. Received: April 7, 2017
  2. Accepted: July 17, 2017
  3. Accepted Manuscript published: July 21, 2017 (version 1)
  4. Version of Record published: August 2, 2017 (version 2)

Copyright

© 2017, Ramond 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. Cyrille Ramond
  2. Nicolas Glaser
  3. Claire Berthault
  4. Jacqueline Ameri
  5. Jeannette Schlichting Kirkegaard
  6. Mattias Hansson
  7. Christian Honoré
  8. Henrik Semb
  9. Raphaël Scharfmann
(2017)
Reconstructing human pancreatic differentiation by mapping specific cell populations during development
eLife 6:e27564.
https://doi.org/10.7554/eLife.27564

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