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Plasticity of Hopx+ type I alveolar cells to regenerate type II cells in the lung

Rajan Jain, Christina E. Barkauskas, Norifumi Takeda, Emily J. Bowie, Haig Aghajanian, Qiaohong Wang, Arun Padmanabhan, Lauren J. Manderfield, Mudit Gupta, Deqiang Li, Li Li, Chinmay M. Trivedi, Brigid L. M. Hogan () and Jonathan A. Epstein ()
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Rajan Jain: Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania
Christina E. Barkauskas: Allergy, and Critical Care Medicine, Duke Medicine
Norifumi Takeda: Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania
Emily J. Bowie: Duke Medicine
Haig Aghajanian: Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania
Qiaohong Wang: Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania
Arun Padmanabhan: Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania
Lauren J. Manderfield: Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania
Mudit Gupta: Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania
Deqiang Li: Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania
Li Li: Allergy, and Critical Care Medicine, Duke Medicine
Chinmay M. Trivedi: Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania
Brigid L. M. Hogan: Duke Medicine
Jonathan A. Epstein: Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: Abstract The plasticity of differentiated cells in adult tissues undergoing repair is an area of intense research. Pulmonary alveolar type II cells produce surfactant and function as progenitors in the adult, demonstrating both self-renewal and differentiation into gas exchanging type I cells. In vivo, type I cells are thought to be terminally differentiated and their ability to give rise to alternate lineages has not been reported. Here we show that Hopx becomes restricted to type I cells during development. However, unexpectedly, lineage-labelled Hopx+ cells both proliferate and generate type II cells during adult alveolar regrowth following partial pneumonectomy. In clonal 3D culture, single Hopx+ type I cells generate organoids composed of type I and type II cells, a process modulated by TGFβ signalling. These findings demonstrate unanticipated plasticity of type I cells and a bidirectional lineage relationship between distinct differentiated alveolar epithelial cell types in vivo and in single-cell culture.

Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7727

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DOI: 10.1038/ncomms7727

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