Abstract
SummaryMulti-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.
Highlights
RESULTSProximal airway epithelial cells (PAECs) play a pivotal role in the host defense in the respiratory tract via mucociliary clearance organized by multi-ciliated airway cells (MCACs) and secretory cells
Using carboxypeptidase M (CPM) as a surface marker of NKX21+-ventralized anterior foregut endoderm cells (VAFECs), we report a three-dimensional differentiation protocol for generating proximal airway epithelial progenitor cell spheroids from CPM+ VAFECs
The directed induction of Multi-ciliated airway cells (MCACs) and of pulmonary neuroendocrine lineage cells was promoted by adding DAPT, a Notch pathway inhibitor
Summary
Multi-ciliated airway cells (MCACs) play a role in mucociliary clearance of the lung. The efficient induction of functional MCACs from human pluripotent stem cells has not yet been reported. 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
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