Type 2 alveolar cells are stem cells in adult lung.
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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.
Mice, Inbred C57BL
Receptor, Platelet-Derived Growth Factor alpha
Adult Stem Cells
Stem Cell Niche
Mice, 129 Strain
Alveolar Epithelial Cells
Published Version (Please cite this version)10.1172/JCI68782
Publication InfoHogan, Brigid; Barkauskas, Christina; Rackley, Craig; Bowie, Emily; Cronce, Michael J; Keene, Douglas R; ... Noble, Paul W (2013). Type 2 alveolar cells are stem cells in adult lung. The Journal of clinical investigation, 123(7). pp. 3025-3036. 10.1172/JCI68782. Retrieved from https://hdl.handle.net/10161/18069.
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Assistant Professor of Medicine
I am a physician-scientist and stem cell biologist focused on understanding the fundamental mechanisms involved in lung injury and repair. I am particularly interested in determining the critical components of the alveolar epithelial stem cell niche and the cellular crosstalk signals that dictate cell identity and behavior during steady state maintenance and repair after injury and infection. I believe this work is fundamental to better understanding the biology of the human lung and the path
George Barth Geller Professor
1. Genetic regulation of embryo development using the mouse as a research model. 2. The role of genes and signaling pathways in directing and co-ordinating the development of the lung. 3. The identity and regulation of the different stem cells in the adult lung and their role in repair, fibrosis and cancer.
Assistant Professor of Medicine
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