Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 17, Pages E1723-E1730Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1403470111
Keywords
differentiation; definitive endoderm; bronchi
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Funding
- Waitt Foundation, National Cancer Institute (NCI) Grant [P30 CA014195-40]
- National Institute of Neurological Disorders and Stroke Grant [P30 NS072031-03]
- NCI Grant [P30 CA014195-40]
- California Institute for Regenerative Medicine (CIRM) Grant [CL-1-0500-1]
- CIRM Postdoctoral Training Fellowship [TG2-01158]
- CIRM-Bridges Internship [TB1-01175]
- CIRM Grant [CL1-00500-1.2]
- Berger Foundation
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Despite therapeutic advancement, pulmonary disease still remains a major cause of morbidity and mortality around the world. Opportunities to study human lung disease either in vivo or in vitro are currently limited. Using induced pluripotent stem cells (iPSCs), we generated mature multiciliated cells in a functional airway epithelium. Robust multiciliogenesis occurred when notch signaling was inhibited and was confirmed by (i) the assembly of multiple pericentrin-stained centrioles at the apical surface, (ii) expression of transcription factor forkhead box protein J1, and (iii) presence of multiple acetylated tubulin-labeled cilia projections in individual cells. Clara, goblet, and basal cells were all present, confirming the generation of a complete polarized epithelial-cell layer. Additionally, cAMP-activated and cystic fibrosis transmembrane regulator inhibitor 172-sensitive cystic fibrosis transmembrane regulator currents were recorded in isolated epithelial cells. Our report demonstrating the generation of mature multiciliated cells in respiratory epithelium from iPSCs is a significant advance toward modeling a number of human respiratory diseases in vitro.
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