Repeated injury promotes tracheobronchial tissue stem cell attrition

Abstract Chronic lung disease has been attributed to stem cell aging and/or exhaustion. We investigated these mechanisms using mouse and human tracheobronchial tissue‐specific stem cells (TSC). In mouse, chromatin labeling and flow cytometry demonstrated that naphthalene (NA) injury activated a subs...

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Autores principales:	Moumita Ghosh, Cynthia L. Hill, Alfahdah Alsudayri, Scott W. Lallier, Don Hayes Jr., Saranga Wijeratne, Zhang Hong Tan, Tendy Chiang, John E. Mahoney, Gianni Carraro, Barry R. Stripp, Susan D. Reynolds
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	airway epithelial stem cell basal cell biological aging chronic lung disease Medicine (General) R5-920 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/9d6a17e6e3c24ef9bf31f1af6b2661cd
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spelling	oai:doaj.org-article:9d6a17e6e3c24ef9bf31f1af6b2661cd2021-12-03T12:11:46ZRepeated injury promotes tracheobronchial tissue stem cell attrition2157-65802157-656410.1002/sctm.21-0032https://doaj.org/article/9d6a17e6e3c24ef9bf31f1af6b2661cd2021-12-01T00:00:00Zhttps://doi.org/10.1002/sctm.21-0032https://doaj.org/toc/2157-6564https://doaj.org/toc/2157-6580Abstract Chronic lung disease has been attributed to stem cell aging and/or exhaustion. We investigated these mechanisms using mouse and human tracheobronchial tissue‐specific stem cells (TSC). In mouse, chromatin labeling and flow cytometry demonstrated that naphthalene (NA) injury activated a subset of TSC. These activated TSC continued to proliferate after the epithelium was repaired and a clone study demonstrated that ~96% of activated TSC underwent terminal differentiation. Despite TSC attrition, epithelial repair after a second NA injury was normal. The second injury accelerated proliferation of previously activated TSC and a nucleotide‐label retention study indicated that the second injury recruited TSC that were quiescent during the first injury. These mouse studies indicate that (a) injury causes selective activation of the TSC pool; (b) activated TSC are predisposed to further proliferation; and (c) the activated state leads to terminal differentiation. In human TSC, repeated proliferation also led to terminal differentiation and depleted the TSC pool. A clone study identified long‐ and short‐lived TSC and showed that short‐lived TSC clones had significantly shorter telomeres than their long‐lived counterparts. The TSC pool was significantly depleted in dyskeratosis congenita donors, who harbor mutations in telomere biology genes. The remaining TSC had short telomeres and short lifespans. Collectively, the mouse and human studies support a model in which epithelial injury increases the biological age of the responding TSC. When applied to chronic lung disease, this model suggests that repeated injury accelerates the biological aging process resulting in abnormal repair and disease initiation.Moumita GhoshCynthia L. HillAlfahdah AlsudayriScott W. LallierDon Hayes Jr.Saranga WijeratneZhang Hong TanTendy ChiangJohn E. MahoneyGianni CarraroBarry R. StrippSusan D. ReynoldsWileyarticleairway epithelial stem cellbasal cellbiological agingchronic lung diseaseMedicine (General)R5-920CytologyQH573-671ENStem Cells Translational Medicine, Vol 10, Iss 12, Pp 1696-1713 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	airway epithelial stem cell basal cell biological aging chronic lung disease Medicine (General) R5-920 Cytology QH573-671
spellingShingle	airway epithelial stem cell basal cell biological aging chronic lung disease Medicine (General) R5-920 Cytology QH573-671 Moumita Ghosh Cynthia L. Hill Alfahdah Alsudayri Scott W. Lallier Don Hayes Jr. Saranga Wijeratne Zhang Hong Tan Tendy Chiang John E. Mahoney Gianni Carraro Barry R. Stripp Susan D. Reynolds Repeated injury promotes tracheobronchial tissue stem cell attrition
description	Abstract Chronic lung disease has been attributed to stem cell aging and/or exhaustion. We investigated these mechanisms using mouse and human tracheobronchial tissue‐specific stem cells (TSC). In mouse, chromatin labeling and flow cytometry demonstrated that naphthalene (NA) injury activated a subset of TSC. These activated TSC continued to proliferate after the epithelium was repaired and a clone study demonstrated that ~96% of activated TSC underwent terminal differentiation. Despite TSC attrition, epithelial repair after a second NA injury was normal. The second injury accelerated proliferation of previously activated TSC and a nucleotide‐label retention study indicated that the second injury recruited TSC that were quiescent during the first injury. These mouse studies indicate that (a) injury causes selective activation of the TSC pool; (b) activated TSC are predisposed to further proliferation; and (c) the activated state leads to terminal differentiation. In human TSC, repeated proliferation also led to terminal differentiation and depleted the TSC pool. A clone study identified long‐ and short‐lived TSC and showed that short‐lived TSC clones had significantly shorter telomeres than their long‐lived counterparts. The TSC pool was significantly depleted in dyskeratosis congenita donors, who harbor mutations in telomere biology genes. The remaining TSC had short telomeres and short lifespans. Collectively, the mouse and human studies support a model in which epithelial injury increases the biological age of the responding TSC. When applied to chronic lung disease, this model suggests that repeated injury accelerates the biological aging process resulting in abnormal repair and disease initiation.
format	article
author	Moumita Ghosh Cynthia L. Hill Alfahdah Alsudayri Scott W. Lallier Don Hayes Jr. Saranga Wijeratne Zhang Hong Tan Tendy Chiang John E. Mahoney Gianni Carraro Barry R. Stripp Susan D. Reynolds
author_facet	Moumita Ghosh Cynthia L. Hill Alfahdah Alsudayri Scott W. Lallier Don Hayes Jr. Saranga Wijeratne Zhang Hong Tan Tendy Chiang John E. Mahoney Gianni Carraro Barry R. Stripp Susan D. Reynolds
author_sort	Moumita Ghosh
title	Repeated injury promotes tracheobronchial tissue stem cell attrition
title_short	Repeated injury promotes tracheobronchial tissue stem cell attrition
title_full	Repeated injury promotes tracheobronchial tissue stem cell attrition
title_fullStr	Repeated injury promotes tracheobronchial tissue stem cell attrition
title_full_unstemmed	Repeated injury promotes tracheobronchial tissue stem cell attrition
title_sort	repeated injury promotes tracheobronchial tissue stem cell attrition
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/9d6a17e6e3c24ef9bf31f1af6b2661cd
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_version_	1718373285231591424

Repeated injury promotes tracheobronchial tissue stem cell attrition

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