@article{6a1558a12da34bf3a31cfdfbb1a70233,
title = "Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells",
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.",
author = "Russell, {John P} and Xinhong Lim and Alice Santambrogio and Val Yianni and Yasmine Kemkem and Bruce Wang and Matthew Fish and Scott Haston and Ana{\"e}lle Grabek and Shirleen Hallang and Lodge, {Emily J} and Patist, {Amanda L} and Andreas Schedl and Patrice Mollard and Roel Nusse and Andoniadou, {Cynthia L}",
note = "Funding Information: This study has been supported by the Medical Research Council (MR/L016729/1, MR/T012153/1) (CLA), The Lister Institute of Preventive Medicine (CLA), the Deutsche Forschungsgemeinschaft (DFG German Research Foundation) (Project Number 314061271 ? TRR 205) (CLA), the Howard Hughes Medical Institute (RN), the Agence Nationale de la Recherche (ANR-18-CE14-0017), and Fondation pour la Recherche M?dicale (DEQ20150331732) (PM). JPR was supported by a Dianna Trebble Endowment Fund Dental Institute Studentship, EJL by the King?s Bioscience Institute and the Guy?s and St Thomas? Charity Prize PhD Programme in Biomedical and Translational Science, and YK by a Project Support Grant from the British Society for Neuroendocrinology. We thank Dr AF Parlow and the National Hormone and Peptide Program (Harbor?University of California, Los Angeles Medical Center) for providing some of the antibodies used in this study and Prof. J Drouin and Prof. S Rhodes for TPIT and PIT1 antibodies respectively. We thank the High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics (funded by Wellcome Trust grant ref-erence 090532/Z/09/Z) for the generation of the sequencing data. For flow sorting and analysis, this research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy?s and St Thomas? NHS Foundation Trust and King?s College London. We thank Marie Isabelle Garcia, Juan Pedro Martinez-Barbera, and Paul Le Tissier for useful discussions and critical comments on the manuscript. Publisher Copyright: {\textcopyright} Russell et al. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = jan,
day = "5",
doi = "10.7554/eLife.59142",
language = "English",
volume = "10",
pages = "1--23",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications, Ltd",
}