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Integrin α6β4 identifies an adult distal lung epithelial population with regenerative potential in mice
Harold A. Chapman,1 Xiaopeng Li,1 Jonathan P. Alexander,1 Alexis Brumwell,1 Walter Lorizio,1 Kevin Tan,1 Arnoud Sonnenberg,2 Ying Wei,1 and Thiennu H. Vu1
1Department of Medicine, Cardiovascular Research Institute, and Lung Biology Center, UCSF, San Francisco, California, USA. 2The Netherlands Cancer Institute, Amsterdam, Netherlands.
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1Department of Medicine, Cardiovascular Research Institute, and Lung Biology Center, UCSF, San Francisco, California, USA. 2The Netherlands Cancer Institute, Amsterdam, Netherlands.
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1Department of Medicine, Cardiovascular Research Institute, and Lung Biology Center, UCSF, San Francisco, California, USA. 2The Netherlands Cancer Institute, Amsterdam, Netherlands.
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1Department of Medicine, Cardiovascular Research Institute, and Lung Biology Center, UCSF, San Francisco, California, USA. 2The Netherlands Cancer Institute, Amsterdam, Netherlands.
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1Department of Medicine, Cardiovascular Research Institute, and Lung Biology Center, UCSF, San Francisco, California, USA. 2The Netherlands Cancer Institute, Amsterdam, Netherlands.
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1Department of Medicine, Cardiovascular Research Institute, and Lung Biology Center, UCSF, San Francisco, California, USA. 2The Netherlands Cancer Institute, Amsterdam, Netherlands.
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1Department of Medicine, Cardiovascular Research Institute, and Lung Biology Center, UCSF, San Francisco, California, USA. 2The Netherlands Cancer Institute, Amsterdam, Netherlands.
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1Department of Medicine, Cardiovascular Research Institute, and Lung Biology Center, UCSF, San Francisco, California, USA. 2The Netherlands Cancer Institute, Amsterdam, Netherlands.
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1Department of Medicine, Cardiovascular Research Institute, and Lung Biology Center, UCSF, San Francisco, California, USA. 2The Netherlands Cancer Institute, Amsterdam, Netherlands.
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First published August 1, 2011 - More info
J Clin Invest. 2011;121(8):3360–3360. https://doi.org/10.1172/JCI59981.
© 2011 The American Society for Clinical Investigation
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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
Original citation: J. Clin. Invest. 2011;121(7):2855–2862. doi:10.1172/JCI57673.
Citation for this corrigendum: J. Clin. Invest. 2011;121(8):3360. doi:10.1172/JCI59981.
In the author list, Arnoud Sonnenberg’s affiliation was incorrect. The correct information appears above.
The authors regret the error.
Copyright © 2020 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)