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

Robert A Jenny, Claire E Hirst, Sue Mei Lim, Adam L Goulburn, Suzanne Jeanine Micallef, Tanya Labonne, Anthony Kicic, Kak-Ming Ling, Stephen Stick, Elizabeth Siew Sun Ng, Alan Osborne Trounson, Antonietta Giudice, Andrew G Elefanty, Edouard G Stanley

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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 human embryonic stem cell line, we developed a serum-free protocol for the generation of NKX2.1+ 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+ endoderm expressed markers indicative of early foregut but lacked genes associated with later stages of respiratory epithelial cell differentiation. Nevertheless, NKX2.1+ endoderm supported the infection and replication of the common respiratory pathogen human rhinovirus HRV1b. Moreover, NKX2.1+ 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.
Original languageEnglish
Pages (from-to)603 - 614
Number of pages12
JournalStem Cells Translational Medicine
Volume4
Issue number6
DOIs
Publication statusPublished - 2015

Cite this

Jenny, R. A., Hirst, C. E., Lim, S. M., Goulburn, A. L., Micallef, S. J., Labonne, T., Kicic, A., Ling, K-M., Stick, S., Ng, E. S. S., Trounson, A. O., Giudice, A., Elefanty, A. G., & Stanley, E. G. (2015). Productive infection of human embryonic stem cell-derived NKX2.1+ respiratory progenitors with human rhinovirus. Stem Cells Translational Medicine, 4(6), 603 - 614. https://doi.org/10.5966/sctm.2014-0274