Type 2 alveolar cells are stem cells in adult lung.
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.
Type
Journal articleSubject
LungCells, Cultured
Stromal Cells
Animals
Mice, Inbred C57BL
Mice, Transgenic
Mice
Receptor, Platelet-Derived Growth Factor alpha
Coculture Techniques
Cell Differentiation
Cell Proliferation
Cell Lineage
Adult Stem Cells
Stem Cell Niche
Lung Injury
Mice, 129 Strain
Alveolar Epithelial Cells
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https://hdl.handle.net/10161/18069Published Version (Please cite this version)
10.1172/JCI68782Publication Info
Barkauskas, Christina E; Cronce, Michael J; Rackley, Craig R; Bowie, Emily J; Keene,
Douglas R; Stripp, Barry R; ... Hogan, Brigid LM (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.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Christina Eleanor Barkauskas
Associate 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
Emily Bowie
Research Assistant, Ph D Student
Brigid L. M. Hogan
Research Professor of Cell Biology
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.
Craig Rackley
Associate Professor of Medicine
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