Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells

  1. John P Russell
  2. Xinhong Lim
  3. Alice Santambrogio
  4. Val Yianni
  5. Yasmine Kemkem
  6. Bruce Wang
  7. Matthew Fish
  8. Scott Haston
  9. Anaëlle Grabek
  10. Shirleen Hallang
  11. Emily J Lodge
  12. Amanda L Patist
  13. Andreas Schedl
  14. Patrice Mollard
  15. Roel Nusse
  16. Cynthia Lilian Andoniadou  Is a corresponding author
  1. King's College London, United Kingdom
  2. Agency for Science, Technology and Research, Singapore
  3. Institut de Génomique Fonctionnelle, France
  4. Howard Hughes Medical Institute, Stanford University School of Medicine, United States
  5. Stanford University, United States
  6. University College London, United Kingdom
  7. Université Côte d'Azur, France
  8. University of Manchester, United Kingdom

Abstract

In response to physiological demand, the pituitary gland generates new hormone-secreting cells from committed progenitor cells throughout life. It remains unclear to what extent pituitary stem cells (PSCs), which uniquely express SOX2, contribute to pituitary growth and renewal. Moreover, neither the signals that drive proliferation nor their sources have been elucidated. We have used genetic approaches in the mouse, showing that the WNT pathway is essential for proliferation of all lineages in the gland. We reveal that SOX2+ stem cells are a key source of WNT ligands. By blocking secretion of WNTs from SOX2+ PSCs in vivo, we demonstrate that proliferation of neighbouring committed progenitor cells declines, demonstrating that progenitor multiplication depends on the paracrine WNT secretion from SOX2+ PSCs. Our results indicate that stem cells can hold additional roles in tissue expansion and homeostasis, acting as paracrine signalling centres to coordinate the proliferation of neighbouring cells.

Data availability

Sequencing data can be accessed through the following link: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA421806

The following data sets were generated

Article and author information

Author details

  1. John P Russell

    Centre for Craniofacial and Regenerative Biology, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  2. Xinhong Lim

    Skin Research Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4725-5161
  3. Alice Santambrogio

    Centre for Craniofacial and Regenerative Biology, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  4. Val Yianni

    Centre for Craniofacial and Regenerative Biology, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9857-7577
  5. Yasmine Kemkem

    Physiology, Institut de Génomique Fonctionnelle, Montpellier, France
    Competing interests
    No competing interests declared.
  6. Bruce Wang

    Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, United States
    Competing interests
    No competing interests declared.
  7. Matthew Fish

    Developmental Biology, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  8. Scott Haston

    Institute of Child Health, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3928-4808
  9. Anaëlle Grabek

    Inserm, CNSR, iBV, Université Côte d'Azur, Nice, France
    Competing interests
    No competing interests declared.
  10. Shirleen Hallang

    Centre for Craniofacial and Regenerative Biology, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  11. Emily J Lodge

    Centre for Craniofacial and Regenerative Biology, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0932-8515
  12. Amanda L Patist

    Centre for Endocrinology and Diabetes, University of Manchester, Manchester, United Kingdom
    Competing interests
    No competing interests declared.
  13. Andreas Schedl

    Inserm, CNSR, iBV, Université Côte d'Azur, Nice, France
    Competing interests
    No competing interests declared.
  14. Patrice Mollard

    Physiology, Institut de Génomique Fonctionnelle, Montpellier, France
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2324-7589
  15. Roel Nusse

    Developmental Biology, Stanford University, Stanford, United States
    Competing interests
    Roel Nusse, Reviewing editor, eLife.
  16. Cynthia Lilian Andoniadou

    Centre for Craniofacial and Regenerative Biology, King's College London, London, United Kingdom
    For correspondence
    cynthia.andoniadou@kcl.ac.uk
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4311-5855

Funding

Medical Research Council (MR/L016729/1)

  • Cynthia Lilian Andoniadou

Medical Research Council (MR/T012153/1)

  • Cynthia Lilian Andoniadou

Deutsche Forschungsgemeinschaft (314061271 - TRR 205)

  • Cynthia Lilian Andoniadou

Howard Hughes Medical Institute

  • Roel Nusse

Agence Nationale de la Recherche (ANR-18-CE14-0017)

  • Patrice Mollard

Fondation pour la Recherche Médicale (DEQ20150331732)

  • Patrice Mollard

Lister Institute of Preventive Medicine

  • Cynthia Lilian Andoniadou

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

Reviewing Editor

  1. Marianne E Bronner, California Institute of Technology, United States

Ethics

Animal experimentation: This study was performed under compliance of the Animals (Scientific Procedures) Act 1986, Home Office License (P5F0A1579) and KCL Biological Safety approval for project 'Function and Regulation of Pituitary Stem Cells in Mammals'

Version history

  1. Received: May 20, 2020
  2. Accepted: January 4, 2021
  3. Accepted Manuscript published: January 5, 2021 (version 1)
  4. Version of Record published: January 12, 2021 (version 2)

Copyright

© 2021, Russell 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. John P Russell
  2. Xinhong Lim
  3. Alice Santambrogio
  4. Val Yianni
  5. Yasmine Kemkem
  6. Bruce Wang
  7. Matthew Fish
  8. Scott Haston
  9. Anaëlle Grabek
  10. Shirleen Hallang
  11. Emily J Lodge
  12. Amanda L Patist
  13. Andreas Schedl
  14. Patrice Mollard
  15. Roel Nusse
  16. Cynthia Lilian Andoniadou
(2021)
Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells
eLife 10:e59142.
https://doi.org/10.7554/eLife.59142

Share this article

https://doi.org/10.7554/eLife.59142

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