Plasticity of Hopx(+) type I alveolar cells to regenerate type II cells in the lung.
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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.
Transforming Growth Factor beta
Green Fluorescent Proteins
Cell Culture Techniques
Published Version (Please cite this version)10.1038/ncomms7727
Publication InfoBarkauskas, Christina; Hogan, Brigid; Bowie, Emily; Jain, Rajan; Takeda, Norifumi; Aghajanian, Haig; ... Epstein, Jonathan A (2015). Plasticity of Hopx(+) type I alveolar cells to regenerate type II cells in the lung. Nature communications, 6(1). pp. 6727. 10.1038/ncomms7727. Retrieved from https://hdl.handle.net/10161/18068.
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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.
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