Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells
- King's College London, United Kingdom
- Agency for Science, Technology and Research, Singapore
- Institut de Génomique Fonctionnelle, France
- Howard Hughes Medical Institute, Stanford University School of Medicine, United States
- Stanford University, United States
- University College London, United Kingdom
- Université Côte d'Azur, France
- 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
Article and author information
Author details
Cynthia Lilian Andoniadou
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
- 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
- Received: May 20, 2020
- Accepted: January 4, 2021
- Accepted Manuscript published: January 5, 2021 (version 1)
- 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.
Metrics
-
- 2,368
- views
-
- 331
- downloads
-
- 24
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
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
Further reading
-
- Neuroscience
- Stem Cells and Regenerative Medicine
While accumulated publications support the existence of neurogenesis in the adult human hippocampus, the homeostasis and developmental potentials of neural stem cells (NSCs) under different contexts remain unclear. Based on our generated single-nucleus atlas of the human hippocampus across neonatal, adult, aging, and injury, we dissected the molecular heterogeneity and transcriptional dynamics of human hippocampal NSCs under different contexts. We further identified new specific neurogenic lineage markers that overcome the lack of specificity found in some well-known markers. Based on developmental trajectory and molecular signatures, we found that a subset of NSCs exhibit quiescent properties after birth, and most NSCs become deep quiescence during aging. Furthermore, certain deep quiescent NSCs are reactivated following stroke injury. Together, our findings provide valuable insights into the development, aging, and reactivation of the human hippocampal NSCs, and help to explain why adult hippocampal neurogenesis is infrequently observed in humans.
-
- Stem Cells and Regenerative Medicine
We developed a 96-well plate assay which allows fast, reproducible, and high-throughput generation of 3D cardiac rings around a deformable optically transparent hydrogel (polyethylene glycol [PEG]) pillar of known stiffness. Human induced pluripotent stem cell-derived cardiomyocytes, mixed with normal human adult dermal fibroblasts in an optimized 3:1 ratio, self-organized to form ring-shaped cardiac constructs. Immunostaining showed that the fibroblasts form a basal layer in contact with the glass, stabilizing the muscular fiber above. Tissues started contracting around the pillar at D1 and their fractional shortening increased until D7, reaching a plateau at 25±1%, that was maintained up to 14 days. The average stress, calculated from the compaction of the central pillar during contractions, was 1.4±0.4 mN/mm2. The cardiac constructs recapitulated expected inotropic responses to calcium and various drugs (isoproterenol, verapamil) as well as the arrhythmogenic effects of dofetilide. This versatile high-throughput assay allows multiple in situ mechanical and structural readouts.
