TY - JOUR
T1 - Productive infection of human embryonic stem cell-derived NKX2.1+ respiratory progenitors with human rhinovirus
AU - Jenny, Robert A
AU - Hirst, Claire E
AU - Lim, Sue Mei
AU - Goulburn, Adam L
AU - Micallef, Suzanne Jeanine
AU - Labonne, Tanya
AU - Kicic, Anthony
AU - Ling, Kak-Ming
AU - Stick, Stephen
AU - Ng, Elizabeth Siew Sun
AU - Trounson, Alan Osborne
AU - Giudice, Antonietta
AU - Elefanty, Andrew G
AU - Stanley, Edouard G
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - http://stemcellstm.alphamedpress.org/content/4/6/603.full.pdf+html
U2 - 10.5966/sctm.2014-0274
DO - 10.5966/sctm.2014-0274
M3 - Article
SN - 2157-6564
VL - 4
SP - 603
EP - 614
JO - Stem Cells Translational Medicine
JF - Stem Cells Translational Medicine
IS - 6
ER -