Generation of multiciliated cells in functional airway epithelia from human induced pluripotent stem cells
Abstract
Pulmonary disease is the third highest cause for morbidity and mortality worldwide. Studies of human lung disease in vivo or in vitro are currently limited. Using induced pluripotent stem cells, we developed a step-wise differentiation protocol ending in an air-liquid interface to generate a pseudostratified polarized layer of endodermal-derived epithelial cells (forkhead box protein A2+ and NK2 homeobox 1+). This layer includes Clara cells with Clara cell 10 kD-positive vesicles, mucin 5A/C-positive goblet cells, multiciliated cells, and isolated cells that have forskolin-induced chloride currents sensitive to cystic fibrosis transmembrane regulator inhibitor 172. The development of this model will enable the future study of many lung diseases (especially those where defective cilia are involved, such as primary ciliary dyskinesia) that have been difficult to study in human models from a developmental perspective.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- April 2014
- DOI:
- 10.1073/pnas.1403470111
- Bibcode:
- 2014PNAS..111E1723F