Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells
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 th...
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doaj-84858b5d6b8d41fa8a6fb5b92aa24fad2021-05-05T22:39:27ZengeLife Sciences Publications LtdeLife2050-084X2021-01-011010.7554/eLife.59142Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cellsJohn P Russell0Xinhong Lim1https://orcid.org/0000-0002-4725-5161Alice Santambrogio2Val Yianni3https://orcid.org/0000-0001-9857-7577Yasmine Kemkem4Bruce Wang5Matthew Fish6Scott Haston7https://orcid.org/0000-0003-3928-4808Anaëlle Grabek8Shirleen Hallang9Emily J Lodge10https://orcid.org/0000-0003-0932-8515Amanda L Patist11Andreas Schedl12Patrice Mollard13https://orcid.org/0000-0002-2324-7589Roel Nusse14Cynthia L Andoniadou15https://orcid.org/0000-0003-4311-5855Centre for Craniofacial and Regenerative Biology, King’s College London, London, United KingdomSkin Research Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, SingaporeCentre for Craniofacial and Regenerative Biology, King’s College London, London, United Kingdom; Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, GermanyCentre for Craniofacial and Regenerative Biology, King’s College London, London, United KingdomInstitute of Functional Genomics (IGF), University of Montpellier, CNRS, Montpellier, FranceHoward Hughes Medical Institute, Stanford University School of Medicine, Department of Developmental Biology, Stanford University School of Medicine, Stanford, United States; Department of Medicine and Liver Center, University of California San Francisco, San Francisco, United StatesHoward Hughes Medical Institute, Stanford University School of Medicine, Department of Developmental Biology, Stanford University School of Medicine, Stanford, United StatesDevelopmental Biology and Cancer, Birth Defects Research Centre, UCL GOS Institute of Child Health, London, United KingdomUniversité Côte d'Azur, Inserm, CNRS, Nice, FranceCentre for Craniofacial and Regenerative Biology, King’s College London, London, United KingdomCentre for Craniofacial and Regenerative Biology, King’s College London, London, United KingdomCentre for Craniofacial and Regenerative Biology, King’s College London, London, United KingdomUniversité Côte d'Azur, Inserm, CNRS, Nice, FranceInstitute of Functional Genomics (IGF), University of Montpellier, CNRS, Montpellier, FranceHoward Hughes Medical Institute, Stanford University School of Medicine, Department of Developmental Biology, Stanford University School of Medicine, Stanford, United StatesCentre for Craniofacial and Regenerative Biology, King’s College London, London, United Kingdom; Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, GermanyIn 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.https://elifesciences.org/articles/59142SOX2WNTparacrine signalpituitary glandfeedforward regulationstem cell |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
John P Russell Xinhong Lim Alice Santambrogio Val Yianni Yasmine Kemkem Bruce Wang Matthew Fish Scott Haston Anaëlle Grabek Shirleen Hallang Emily J Lodge Amanda L Patist Andreas Schedl Patrice Mollard Roel Nusse Cynthia L Andoniadou |
spellingShingle |
John P Russell Xinhong Lim Alice Santambrogio Val Yianni Yasmine Kemkem Bruce Wang Matthew Fish Scott Haston Anaëlle Grabek Shirleen Hallang Emily J Lodge Amanda L Patist Andreas Schedl Patrice Mollard Roel Nusse Cynthia L Andoniadou Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells eLife SOX2 WNT paracrine signal pituitary gland feedforward regulation stem cell |
author_facet |
John P Russell Xinhong Lim Alice Santambrogio Val Yianni Yasmine Kemkem Bruce Wang Matthew Fish Scott Haston Anaëlle Grabek Shirleen Hallang Emily J Lodge Amanda L Patist Andreas Schedl Patrice Mollard Roel Nusse Cynthia L Andoniadou |
author_sort |
John P Russell |
title |
Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells |
title_short |
Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells |
title_full |
Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells |
title_fullStr |
Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells |
title_full_unstemmed |
Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells |
title_sort |
pituitary stem cells produce paracrine wnt signals to control the expansion of their descendant progenitor cells |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2021-01-01 |
description |
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. |
topic |
SOX2 WNT paracrine signal pituitary gland feedforward regulation stem cell |
url |
https://elifesciences.org/articles/59142 |
work_keys_str_mv |
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