Unknown

Dataset Information

0

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


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-K1high 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-K1high 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.

SUBMITTER: Kathiriya JJ 

PROVIDER: S-EPMC7233183 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Kathiriya Jaymin J JJ   Brumwell Alexis N AN   Jackson Julia R JR   Tang Xiaodan X   Chapman Harold A HA  

Cell stem cell 20200123 3


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 expressi  ...[more]

Similar Datasets

| S-EPMC5269679 | biostudies-literature
| S-EPMC4741569 | biostudies-literature
| S-EPMC7328256 | biostudies-literature
| S-EPMC7531137 | biostudies-literature
| S-EPMC6085545 | biostudies-literature
| S-EPMC3547097 | biostudies-literature
| S-EPMC6524168 | biostudies-literature
| S-EPMC2739774 | biostudies-literature
| S-EPMC8220578 | biostudies-literature
2018-04-30 | GSE111557 | GEO