Cargando…
Distal lung epithelial progenitor cell function declines with age
Tissue stem cell exhaustion is a key hallmark of aging, and in this study, we characterised its manifestation in the distal lung. We compared the lungs of 3- and 22-month old mice. We examined the gross morphological changes in these lungs, the density and function of epithelial progenitor populatio...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319976/ https://www.ncbi.nlm.nih.gov/pubmed/32591591 http://dx.doi.org/10.1038/s41598-020-66966-y |
_version_ | 1783551151705161728 |
---|---|
author | Watson, Julie K. Sanders, Philip Dunmore, Rebecca Rosignoli, Guglielmo Julé, Yvon Rawlins, Emma L. Mustelin, Tomas May, Richard Clarke, Deborah Finch, Donna K. |
author_facet | Watson, Julie K. Sanders, Philip Dunmore, Rebecca Rosignoli, Guglielmo Julé, Yvon Rawlins, Emma L. Mustelin, Tomas May, Richard Clarke, Deborah Finch, Donna K. |
author_sort | Watson, Julie K. |
collection | PubMed |
description | Tissue stem cell exhaustion is a key hallmark of aging, and in this study, we characterised its manifestation in the distal lung. We compared the lungs of 3- and 22-month old mice. We examined the gross morphological changes in these lungs, the density and function of epithelial progenitor populations and the epithelial gene expression profile. Bronchioles became smaller in their cross-sectional area and diameter. Using long-term EdU incorporation analysis and immunohistochemistry, we found that bronchiolar cell density remained stable with aging, but inferred rates of bronchiolar club progenitor cell self-renewal and differentiation were reduced, indicative of an overall slowdown in cellular turnover. Alveolar Type II progenitor cell density and self-renewal were maintained per unit tissue area with aging, but rates of inferred differentiation into Type I cells, and indeed overall density of Type I cells was reduced. Microarray analysis revealed age-related changes in multiple genes, including some with roles in proliferation and differentiation, and in IGF and TGFβ signalling pathways. By characterising how lung stem cell dynamics change with aging, this study will elucidate how they contribute to age-related loss of pulmonary function, and pathogenesis of common age-related pulmonary diseases. |
format | Online Article Text |
id | pubmed-7319976 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-73199762020-06-30 Distal lung epithelial progenitor cell function declines with age Watson, Julie K. Sanders, Philip Dunmore, Rebecca Rosignoli, Guglielmo Julé, Yvon Rawlins, Emma L. Mustelin, Tomas May, Richard Clarke, Deborah Finch, Donna K. Sci Rep Article Tissue stem cell exhaustion is a key hallmark of aging, and in this study, we characterised its manifestation in the distal lung. We compared the lungs of 3- and 22-month old mice. We examined the gross morphological changes in these lungs, the density and function of epithelial progenitor populations and the epithelial gene expression profile. Bronchioles became smaller in their cross-sectional area and diameter. Using long-term EdU incorporation analysis and immunohistochemistry, we found that bronchiolar cell density remained stable with aging, but inferred rates of bronchiolar club progenitor cell self-renewal and differentiation were reduced, indicative of an overall slowdown in cellular turnover. Alveolar Type II progenitor cell density and self-renewal were maintained per unit tissue area with aging, but rates of inferred differentiation into Type I cells, and indeed overall density of Type I cells was reduced. Microarray analysis revealed age-related changes in multiple genes, including some with roles in proliferation and differentiation, and in IGF and TGFβ signalling pathways. By characterising how lung stem cell dynamics change with aging, this study will elucidate how they contribute to age-related loss of pulmonary function, and pathogenesis of common age-related pulmonary diseases. Nature Publishing Group UK 2020-06-26 /pmc/articles/PMC7319976/ /pubmed/32591591 http://dx.doi.org/10.1038/s41598-020-66966-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Watson, Julie K. Sanders, Philip Dunmore, Rebecca Rosignoli, Guglielmo Julé, Yvon Rawlins, Emma L. Mustelin, Tomas May, Richard Clarke, Deborah Finch, Donna K. Distal lung epithelial progenitor cell function declines with age |
title | Distal lung epithelial progenitor cell function declines with age |
title_full | Distal lung epithelial progenitor cell function declines with age |
title_fullStr | Distal lung epithelial progenitor cell function declines with age |
title_full_unstemmed | Distal lung epithelial progenitor cell function declines with age |
title_short | Distal lung epithelial progenitor cell function declines with age |
title_sort | distal lung epithelial progenitor cell function declines with age |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319976/ https://www.ncbi.nlm.nih.gov/pubmed/32591591 http://dx.doi.org/10.1038/s41598-020-66966-y |
work_keys_str_mv | AT watsonjuliek distallungepithelialprogenitorcellfunctiondeclineswithage AT sandersphilip distallungepithelialprogenitorcellfunctiondeclineswithage AT dunmorerebecca distallungepithelialprogenitorcellfunctiondeclineswithage AT rosignoliguglielmo distallungepithelialprogenitorcellfunctiondeclineswithage AT juleyvon distallungepithelialprogenitorcellfunctiondeclineswithage AT rawlinsemmal distallungepithelialprogenitorcellfunctiondeclineswithage AT mustelintomas distallungepithelialprogenitorcellfunctiondeclineswithage AT mayrichard distallungepithelialprogenitorcellfunctiondeclineswithage AT clarkedeborah distallungepithelialprogenitorcellfunctiondeclineswithage AT finchdonnak distallungepithelialprogenitorcellfunctiondeclineswithage |