Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Integrin α6β4 identifies an adult distal lung epithelial population with regenerative potential in mice
Harold A. Chapman, … , Ying Wei, Thiennu H. Vu
Harold A. Chapman, … , Ying Wei, Thiennu H. Vu
Published June 23, 2011
Citation Information: J Clin Invest. 2011;121(7):2855-2862. https://doi.org/10.1172/JCI57673.
View: Text | PDF | Corrigendum
Research Article

Integrin α6β4 identifies an adult distal lung epithelial population with regenerative potential in mice

  • Text
  • PDF
Abstract

Laminins and their integrin receptors are implicated in epithelial cell differentiation and progenitor cell maintenance. We report here that a previously unrecognized subpopulation of mouse alveolar epithelial cells (AECs) expressing the laminin receptor α6β4, but little or no pro–surfactant C (pro-SPC), is endowed with regenerative potential. Ex vivo, this subpopulation expanded clonally as progenitors but also differentiated toward mature cell types. Integrin β4 itself was not required for AEC proliferation or differentiation. An in vivo embryonic lung organoid assay, which we believe to be novel, was used to show that purified β4+ adult AECs admixed with E14.5 lung single-cell suspensions and implanted under kidney capsules self-organized into distinct Clara cell 10-kDa secretory protein (CC10+) airway-like and SPC+ saccular structures within 6 days. Using a bleomycin model of lung injury and an SPC-driven inducible cre to fate-map AECs, we found the majority of type II AECs in fibrotic areas were not derived from preexisting type II AECs, demonstrating that SPC– progenitor cells replenished type II AECs during repair. Our findings support the idea that there is a stable AEC progenitor population in the adult lung, provide in vivo evidence of AEC progenitor cell differentiation after parenchymal injury, and identify a strong candidate progenitor cell for maintenance of type II AECs during lung repair.

Authors

Harold A. Chapman, Xiaopeng Li, Jonathan P. Alexander, Alexis Brumwell, Walter Lorizio, Kevin Tan, Arnoud Sonnenberg, Ying Wei, Thiennu H. Vu

×

Figure 2

Ex vivo proliferation and clonal expansion of β4+ AECs.

Options: View larger image (or click on image) Download as PowerPoint
Ex vivo proliferation and clonal expansion of β4+ AECs.
   
(A) Immunobl...
(A) Immunoblot verifying separation of β4+ and β4– cells. (B) Phase-contrast images of β4+ and β4– AECs from WT mice cultured 7 days on Matrigel revealed large clusters only in the β4+ population. Ki67 and pro-SPC staining of cultured β4+ and β4– AECs revealed proliferation of β4+ cells and appearance of SPC+ cells, especially in the smaller clusters. Cells were initially SPClo or SPC–. β4– AECs were strongly SPC+ and had little or no proliferation. The same number of β4+ and β4– cells were initially seeded. (C) BrdU assay at 24 hours (Chemicon) confirmed that greater than 90% of the proliferation among AECs resided in the β4+ fraction. WT, cell mixture before sorting. (D) AECs from floxed β4 mice treated ex vivo with adenovirus encoding cre recombinase. Developing clusters (>15 per culture well) were either all β4+ or all β4–. Scale bars: 50 μm.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts