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Directed Induction of Functional Multi-ciliated Cells in Proximal Airway Epithelial Spheroids from Human Pluripotent Stem Cells.
- Source :
-
Stem cell reports [Stem Cell Reports] 2016 Jan 12; Vol. 6 (1), pp. 18-25. Date of Electronic Publication: 2015 Dec 24. - Publication Year :
- 2016
-
Abstract
- Multi-ciliated airway cells (MCACs) play a role in mucociliary clearance of the lung. However, the efficient induction of functional MCACs from human pluripotent stem cells has not yet been reported. Using carboxypeptidase M (CPM) as a surface marker of NKX2-1(+)-ventralized anterior foregut endoderm cells (VAFECs), we report a three-dimensional differentiation protocol for generating proximal airway epithelial progenitor cell spheroids from CPM(+) VAFECs. These spheroids could be induced to generate MCACs and other airway lineage cells without alveolar epithelial cells. Furthermore, the directed induction of MCACs and of pulmonary neuroendocrine lineage cells was promoted by adding DAPT, a Notch pathway inhibitor. The induced MCACs demonstrated motile cilia with a "9 + 2" microtubule arrangement and dynein arms capable of beating and generating flow for mucociliary transport. This method is expected to be useful for future studies on human airway disease modeling and regenerative medicine.<br /> (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Cell Culture Techniques
Cell Differentiation genetics
Cell Line
Cell Lineage genetics
Cells, Cultured
Dyneins metabolism
Endoderm cytology
Endoderm metabolism
Epithelial Cells metabolism
Epithelial Cells ultrastructure
GPI-Linked Proteins metabolism
Gene Expression Regulation, Developmental
Humans
Intestines cytology
Metalloendopeptidases metabolism
Microscopy, Electron
Microscopy, Fluorescence
Microtubules metabolism
Pluripotent Stem Cells metabolism
Reverse Transcriptase Polymerase Chain Reaction
Spheroids, Cellular metabolism
Spheroids, Cellular ultrastructure
Cilia
Epithelial Cells cytology
Lung cytology
Pluripotent Stem Cells cytology
Spheroids, Cellular cytology
Subjects
Details
- Language :
- English
- ISSN :
- 2213-6711
- Volume :
- 6
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Stem cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 26724905
- Full Text :
- https://doi.org/10.1016/j.stemcr.2015.11.010