Authors:
Jenny RA, Hirst C, Lim SM, Goulburn AL, Micallef SJ, Labonne T,... Kicic A,... Stick SM, et al.
Authors notes:
Stem Cells Transl Med. 2015;4(6):603-14.
Keywords:
Differentiation, GFP, HRV, Human embryonic stem cells, Lung, NKX2.1, Respiratory endoderm, Rhinovirus, Human rhinovirus sp., Mus
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 humanembryonic 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+ endo-derm 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.