Cited by 247Neonatal Respiratory Health ResearchTissue Engineering and Regenerative MedicineLiver physiology and pathology

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Distinct Airway Epithelial Stem Cells Hide among Club Cells but Mobilize to Promote Alveolar Regeneration

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Kathiriya, Jaymin J., Brumwell, Alexis N., Jackson, Julia R., Tang, Xiaodan, Chapman, Harold A.·2020·Cell Stem Cell

DOI 10.1016/j.stem.2019.12.014PMC PMC7233183

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Abstract

Lung injury activates specialized adult epithelial progenitors to regenerate the epithelium. Depending on the extent of injury, both remaining alveolar type II cells (AEC2s) and distal airway stem/progenitors mobilize to cover denuded alveoli and restore normal barriers. The major source of airway stem/progenitors other than basal-like cells remains uncertain. Here, we define a distinct subpopulation (∼5%) of club-like lineage-negative epithelial progenitors (LNEPs) marked by high H2-K1 expression critical for alveolar repair. Quiescent H2-K1 high cells account for virtually all in vitro regenerative activity of airway lineages. After bleomycin injury, H2-K1 cells expand and differentiate in vivo to alveolar lineages. However, injured H2-K1 cells eventually develop impaired self-renewal with features of senescence, limiting complete repair. Normal H2-K1 high cells transplanted into injured lungs differentiate into alveolar cells and rescue lung function. These findings indicate that small subpopulations of specialized stem/progenitors are required for effective lung regeneration and are a potential therapeutic adjunct after major lung injury.

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Authors: Kathiriya, J. J., Brumwell, A. N., Jackson, J. R., Tang, X., & Chapman, H. A.
Affiliations: University of California, San Francisco (US)
Shanghai Medical College of Fudan University (CN)
Corresponding author: Chapman, Harold A.
ORCID: Kathiriya, Jaymin J.
Brumwell, Alexis N.
Chapman, Harold A.
Venue: Cell Stem Cell
Publisher: Elsevier BV
Published: 2020-03
Volume: 26
Issue: 3
Pages: 346-358.e4
ISSN: 1875-9777 (ISSN-L)
1934-5909
DOI: 10.1016/j.stem.2019.12.014
PMC: PMC7233183
OpenAlex: W3002314962
Cited by: 246
References: 46
Citations by year: 2026: 26 · 2025: 38 · 2024: 42 · 2023: 48 · 2022: 33 · 2021: 33 · 2020: 26
FWCI: 19.70
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 369 d)
Locations: Cell stem cell (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Heart, Lung, and Blood Institute
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Neonatal Respiratory Health Research
Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords: Clara cells, alveolar regeneration, lung injury, alveolar type II cells, epithelial progenitors, cellular senescence, self-renewal, cell transplantation
MeSH terms: Cell Differentiation, Epithelial Cells, Humans, Lung, Stem Cells, Lung Injury, Alveolar Epithelial Cells

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Distinct Airway Epithelial Stem Cells Hide among Club Cells but Mobilize to Promote Alveolar Regeneration

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