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Type 2 alveolar cells are stem cells in adult lung
Christina E. Barkauskas, … , Paul W. Noble, Brigid L.M. Hogan
Christina E. Barkauskas, … , Paul W. Noble, Brigid L.M. Hogan
Published June 10, 2013
Citation Information: J Clin Invest. 2013;123(7):3025-3036. https://doi.org/10.1172/JCI68782.
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Research Article Pulmonology Article has an altmetric score of 61

Type 2 alveolar cells are stem cells in adult lung

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Abstract

Gas exchange in the lung occurs within alveoli, air-filled sacs composed of type 2 and type 1 epithelial cells (AEC2s and AEC1s), capillaries, and various resident mesenchymal cells. Here, we use a combination of in vivo clonal lineage analysis, different injury/repair systems, and in vitro culture of purified cell populations to obtain new information about the contribution of AEC2s to alveolar maintenance and repair. Genetic lineage-tracing experiments showed that surfactant protein C–positive (SFTPC-positive) AEC2s self renew and differentiate over about a year, consistent with the population containing long-term alveolar stem cells. Moreover, if many AEC2s were specifically ablated, high-resolution imaging of intact lungs showed that individual survivors undergo rapid clonal expansion and daughter cell dispersal. Individual lineage-labeled AEC2s placed into 3D culture gave rise to self-renewing “alveolospheres,” which contained both AEC2s and cells expressing multiple AEC1 markers, including HOPX, a new marker for AEC1s. Growth and differentiation of the alveolospheres occurred most readily when cocultured with primary PDGFRα+ lung stromal cells. This population included lipofibroblasts that normally reside close to AEC2s and may therefore contribute to a stem cell niche in the murine lung. Results suggest that a similar dynamic exists between AEC2s and mesenchymal cells in the human lung.

Authors

Christina E. Barkauskas, Michael J. Cronce, Craig R. Rackley, Emily J. Bowie, Douglas R. Keene, Barry R. Stripp, Scott H. Randell, Paul W. Noble, Brigid L.M. Hogan

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Figure 6

Recapitulating the AEC2 stem cell niche.

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Recapitulating the AEC2 stem cell niche.
Sections from adult Pdgfra-H2B:...
Sections from adult Pdgfra-H2B:GFP lungs were stained for neutral lipid and/or SFTPC. (A) LipidTOX staining colocalizes with high-intensity GFP+ cells in alveoli, but not with lower-intensity GFP+ cells (arrows) in the bronchiolar wall. (B) LipidTOX+, PDGFRA-GFP+ cells are closely apposed to SFTPC+ AEC2s (purple). (C) FACS-sorted PDGFRA-GFPhi cells are also positive for LipidTOX. (D) LipidTox+ PDGFRA-GFP+ cells express the intermediate filament protein desmin. (E and F) Multiple PDGFRA-GFP+;desmin+ cells are interspersed throughout an alveolosphere at day 21. (G) TEM of alveolosphere reveals multiple lipid-filled cells (L) adjacent to lamellar body–containing AEC2s. Scale bars: 50 μm (A–F); 2 μm (G).

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

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