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标题：Prominin 1 and Notch regulate ciliary length and dynamics in multiciliated cells of the airway epithelium
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作者：Carlos F.H. Serra ; Helu Liu ; Jun Qian 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：8
页码：1-20
DOI：10.1016/j.isci.2022.104751
语种：English
出版社：Elsevier
摘要：SummaryDifferences in ciliary morphology and dynamics among multiciliated cells of the respiratory tract contribute to efficient mucociliary clearance. Nevertheless, little is known about how these phenotypic differences are established. We show that Prominin 1 (Prom1), a transmembrane protein widely used as stem cell marker, is crucial to this process. During airway differentiation, Prom1 becomes restricted to multiciliated cells, where it is expressed at distinct levels along the proximal-distal axis of the airways. Prom1 is induced by Notch in multiciliated cells, and Notch inactivation abolishes this gradient of expression. Prom1 was not required for multicilia formation, but when inactivated resulted in longer cilia that beat at a lower frequency. Disruption of Notch resulted in opposite effects and suggested that Notch fine-tunes Prom1 levels to regulate the multiciliated cell phenotype and generate diversity among these cells. This mechanism could contribute to the innate defense of the lung and help prevent pulmonary disease.Graphical abstractDisplay OmittedHighlights•Prom1 is expressed in a proximal-distal gradient in developing airways•Prom1 is induced in post-specified multiciliated cells by low levels of Notch activation•Prom1 modulates cilia length and ciliary beating frequency in multiciliated cells•Notch fine-tunes Prom1 levels to generate multiciliated cell diversity in the airwaysCell biology; Molecular physiology