Productive infection of human embryonic stem cell-derived NKX2.1+ respiratory progenitors with human rhinovirus

© AlphaMed Press 2015. Airway epithelial cells generated from pluripotent stem cells (PSCs) represent a resource for research into a variety of human respiratory conditions, including those resulting from infection with common human pathogens. Using an NKX2.1-GFP reporter humanembryonic stem cell li...

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Bibliographic Details
Main Authors: Jenny, R.A., Hirst, C., Lim, S.M., Goulburn, A.L., Micallef, S.J., Labonne, T., Kicic, Anthony, Ling, K.M., Stick, S.M., Ng, E.S., Trounson, A., Giudice, A., Elefanty, A.G., Stanley, E.G.
Format: Journal Article
Language:English
Published: ALPHAMED PRESS 2015
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Online Access:http://hdl.handle.net/20.500.11937/76816
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Summary:© AlphaMed Press 2015. Airway epithelial cells generated from pluripotent stem cells (PSCs) represent a resource for research into a variety of human respiratory conditions, including those resulting from infection with common human pathogens. Using an NKX2.1-GFP reporter humanembryonic stem cell line, wede-veloped a serum-free protocol for the generation of NKX2.1 < sup > + < /sup > endoderm that, when transplanted into immunodeficient mice, matured into respiratory cell types identified by expression of CC10, MUC5AC, and surfactant proteins. Gene profiling experiments indicated that day 10 NKX2.1 < sup > + < /sup > endo-derm expressed markers indicative of early foregut but lacked genes associated with later stages of respiratory epithelial cell differentiation. Nevertheless, NKX2.1 < sup > + < /sup > endoderm supported the infection and replication of the common respiratory pathogen human rhinovirus HRV1b. Moreover, NKX2.1 < sup > + < /sup > endoderm upregulated expression of IL-6, IL-8, and IL-1B in response to infection, a characteristic of human airway epithelial cells. Our experiments provide proof of principle for the use of PSC-derived respiratory epithelial cells in the study of cell-virus interactions.