title: Productive Infection of Human Embryonic Stem Cell-Derived NKX2.1+ Respiratory Progenitors with Human Rhinovirus.
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.
  
  
  CONCLUSIONS
  This report provides proof-of-principle experiments demonstrating, for the first time, that human respiratory progenitor cells derived from stem cells in the laboratory can be productively infected with human rhinovirus, the predominant cause of the common cold.
authors: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia; Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Telethon Kids Institute, Centre for Health Research, School of Paediatrics and Child Health, Centre for Health Research, and Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia; Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia; Richie Centre, Monash Prince Henry's Medical Research Institute, Clayton, Victoria, Australia.
authors: Robert A
authors: RA
authors: Jenny
authors: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia; Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Telethon Kids Institute, Centre for Health Research, School of Paediatrics and Child Health, Centre for Health Research, and Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia; Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia; Richie Centre, Monash Prince Henry's Medical Research Institute, Clayton, Victoria, Australia.
authors: Claire
authors: C
authors: Hirst
authors: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia; Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Telethon Kids Institute, Centre for Health Research, School of Paediatrics and Child Health, Centre for Health Research, and Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia; Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia; Richie Centre, Monash Prince Henry's Medical Research Institute, Clayton, Victoria, Australia.
authors: Sue Mei
authors: SM
authors: Lim
authors: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia; Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Telethon Kids Institute, Centre for Health Research, School of Paediatrics and Child Health, Centre for Health Research, and Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia; Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia; Richie Centre, Monash Prince Henry's Medical Research Institute, Clayton, Victoria, Australia.
authors: Adam L
authors: AL
authors: Goulburn
authors: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia; Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Telethon Kids Institute, Centre for Health Research, School of Paediatrics and Child Health, Centre for Health Research, and Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia; Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia; Richie Centre, Monash Prince Henry's Medical Research Institute, Clayton, Victoria, Australia.
authors: Suzanne J
authors: SJ
authors: Micallef
authors: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia; Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Telethon Kids Institute, Centre for Health Research, School of Paediatrics and Child Health, Centre for Health Research, and Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia; Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia; Richie Centre, Monash Prince Henry's Medical Research Institute, Clayton, Victoria, Australia.
authors: Tanya
authors: T
authors: Labonne
authors: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia; Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Telethon Kids Institute, Centre for Health Research, School of Paediatrics and Child Health, Centre for Health Research, and Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia; Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia; Richie Centre, Monash Prince Henry's Medical Research Institute, Clayton, Victoria, Australia.
authors: Anthony
authors: A
authors: Kicic
authors: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia; Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Telethon Kids Institute, Centre for Health Research, School of Paediatrics and Child Health, Centre for Health Research, and Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia; Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia; Richie Centre, Monash Prince Henry's Medical Research Institute, Clayton, Victoria, Australia.
authors: Kak-Ming
authors: KM
authors: Ling
authors: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia; Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Telethon Kids Institute, Centre for Health Research, School of Paediatrics and Child Health, Centre for Health Research, and Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia; Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia; Richie Centre, Monash Prince Henry's Medical Research Institute, Clayton, Victoria, Australia.
authors: Stephen M
authors: SM
authors: Stick
authors: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia; Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Telethon Kids Institute, Centre for Health Research, School of Paediatrics and Child Health, Centre for Health Research, and Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia; Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia; Richie Centre, Monash Prince Henry's Medical Research Institute, Clayton, Victoria, Australia.
authors: Elizabeth S
authors: ES
authors: Ng
authors: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia; Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Telethon Kids Institute, Centre for Health Research, School of Paediatrics and Child Health, Centre for Health Research, and Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia; Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia; Richie Centre, Monash Prince Henry's Medical Research Institute, Clayton, Victoria, Australia.
authors: Alan
authors: A
authors: Trounson
authors: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia; Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Telethon Kids Institute, Centre for Health Research, School of Paediatrics and Child Health, Centre for Health Research, and Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia; Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia; Richie Centre, Monash Prince Henry's Medical Research Institute, Clayton, Victoria, Australia.
authors: Antonietta
authors: A
authors: Giudice
authors: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia; Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Telethon Kids Institute, Centre for Health Research, School of Paediatrics and Child Health, Centre for Health Research, and Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia; Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia; Richie Centre, Monash Prince Henry's Medical Research Institute, Clayton, Victoria, Australia.
authors: Andrew G
authors: AG
authors: Elefanty
authors: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia; Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Telethon Kids Institute, Centre for Health Research, School of Paediatrics and Child Health, Centre for Health Research, and Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia; Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia; Richie Centre, Monash Prince Henry's Medical Research Institute, Clayton, Victoria, Australia ed.stanley@mcri.edu.au.
authors: Edouard G
authors: EG
authors: Stanley
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009687:Nuclear Proteins; D010850:Picornaviridae Infections / Q000401:mortality* / Q000473:pathology; D020545:Respiratory Mucosa / Q000378:metabolism / Q000821:virology*; D012229:Rhinovirus / Q000502:physiology*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors
chemical_list: C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors
keywords: Differentiation; GFP; HRV; Human embryonic stem cells; Lung; NKX2.1; Respiratory endoderm; Rhinovirus