Stochastic homeostasis in human airway epithelium is achieved by neutral competition of basal cell progenitors
Lineage tracing approaches have provided new insights into the cellular mechanisms that support tissue homeostasis in mice. However, the relevance of these discoveries to human epithelial homeostasis and its alterations in disease is unknown. By developing a novel quantitative approach for the analy...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2013-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/00966 |
| _version_ | 1828204083788382208 |
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| author | Vitor H Teixeira Parthiban Nadarajan Trevor A Graham Christodoulos P Pipinikas James M Brown Mary Falzon Emma Nye Richard Poulsom David Lawrence Nicholas A Wright Stuart McDonald Adam Giangreco Benjamin D Simons Sam M Janes |
| author_facet | Vitor H Teixeira Parthiban Nadarajan Trevor A Graham Christodoulos P Pipinikas James M Brown Mary Falzon Emma Nye Richard Poulsom David Lawrence Nicholas A Wright Stuart McDonald Adam Giangreco Benjamin D Simons Sam M Janes |
| author_sort | Vitor H Teixeira |
| collection | DOAJ |
| description | Lineage tracing approaches have provided new insights into the cellular mechanisms that support tissue homeostasis in mice. However, the relevance of these discoveries to human epithelial homeostasis and its alterations in disease is unknown. By developing a novel quantitative approach for the analysis of somatic mitochondrial mutations that are accumulated over time, we demonstrate that the human upper airway epithelium is maintained by an equipotent basal progenitor cell population, in which the chance loss of cells due to lineage commitment is perfectly compensated by the duplication of neighbours, leading to “neutral drift” of the clone population. Further, we show that this process is accelerated in the airways of smokers, leading to intensified clonal consolidation and providing a background for tumorigenesis. This study provides a benchmark to show how somatic mutations provide quantitative information on homeostatic growth in human tissues, and a platform to explore factors leading to dysregulation and disease. |
| first_indexed | 2024-04-12T12:16:30Z |
| format | Article |
| id | doaj.art-31a109e4039d4bf1af09a1a9bc470d72 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:16:30Z |
| publishDate | 2013-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-31a109e4039d4bf1af09a1a9bc470d722022-12-22T03:33:24ZengeLife Sciences Publications LtdeLife2050-084X2013-10-01210.7554/eLife.00966Stochastic homeostasis in human airway epithelium is achieved by neutral competition of basal cell progenitorsVitor H Teixeira0Parthiban Nadarajan1Trevor A Graham2Christodoulos P Pipinikas3James M Brown4Mary Falzon5Emma Nye6Richard Poulsom7David Lawrence8Nicholas A Wright9Stuart McDonald10Adam Giangreco11Benjamin D Simons12Sam M Janes13Lungs for Living Research Centre, UCL Respiratory, University College London, London, United KingdomLungs for Living Research Centre, UCL Respiratory, University College London, London, United KingdomHistopathology Laboratory, Cancer Research UK London Research Institute, London, United Kingdom; Centre for Evolution and Cancer, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, United StatesLungs for Living Research Centre, UCL Respiratory, University College London, London, United KingdomLungs for Living Research Centre, UCL Respiratory, University College London, London, United KingdomDepartment of Histopathology, University College Hospital London, London, United KingdomExperimental Histopathology Laboratory, Cancer Research UK London Research Institute, London, United KingdomHistopathology Laboratory, Cancer Research UK London Research Institute, London, United Kingdom; Centre for Digestive Diseases, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, London, United KingdomDepartment of Cardiothoracic Surgery, The Heart Hospital, London, United KingdomHistopathology Laboratory, Cancer Research UK London Research Institute, London, United Kingdom; Centre for Tumour Biology, Barts Cancer Institute, John Vane Science Centre, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, London, United KingdomHistopathology Laboratory, Cancer Research UK London Research Institute, London, United Kingdom; Centre for Tumour Biology, Barts Cancer Institute, John Vane Science Centre, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, London, United KingdomLungs for Living Research Centre, UCL Respiratory, University College London, London, United KingdomCavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, United Kingdom; The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust–Medical Research Council Stem Cell Institute, University of Cambridge, United KingdomLungs for Living Research Centre, UCL Respiratory, University College London, London, United KingdomLineage tracing approaches have provided new insights into the cellular mechanisms that support tissue homeostasis in mice. However, the relevance of these discoveries to human epithelial homeostasis and its alterations in disease is unknown. By developing a novel quantitative approach for the analysis of somatic mitochondrial mutations that are accumulated over time, we demonstrate that the human upper airway epithelium is maintained by an equipotent basal progenitor cell population, in which the chance loss of cells due to lineage commitment is perfectly compensated by the duplication of neighbours, leading to “neutral drift” of the clone population. Further, we show that this process is accelerated in the airways of smokers, leading to intensified clonal consolidation and providing a background for tumorigenesis. This study provides a benchmark to show how somatic mutations provide quantitative information on homeostatic growth in human tissues, and a platform to explore factors leading to dysregulation and disease.https://elifesciences.org/articles/00966Human lineage tracingmtDNA mutationlung basal progenitor stem cellstochastic homeostasisairway |
| spellingShingle | Vitor H Teixeira Parthiban Nadarajan Trevor A Graham Christodoulos P Pipinikas James M Brown Mary Falzon Emma Nye Richard Poulsom David Lawrence Nicholas A Wright Stuart McDonald Adam Giangreco Benjamin D Simons Sam M Janes Stochastic homeostasis in human airway epithelium is achieved by neutral competition of basal cell progenitors eLife Human lineage tracing mtDNA mutation lung basal progenitor stem cell stochastic homeostasis airway |
| title | Stochastic homeostasis in human airway epithelium is achieved by neutral competition of basal cell progenitors |
| title_full | Stochastic homeostasis in human airway epithelium is achieved by neutral competition of basal cell progenitors |
| title_fullStr | Stochastic homeostasis in human airway epithelium is achieved by neutral competition of basal cell progenitors |
| title_full_unstemmed | Stochastic homeostasis in human airway epithelium is achieved by neutral competition of basal cell progenitors |
| title_short | Stochastic homeostasis in human airway epithelium is achieved by neutral competition of basal cell progenitors |
| title_sort | stochastic homeostasis in human airway epithelium is achieved by neutral competition of basal cell progenitors |
| topic | Human lineage tracing mtDNA mutation lung basal progenitor stem cell stochastic homeostasis airway |
| url | https://elifesciences.org/articles/00966 |
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