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JAG1-Mediated Notch Signaling Regulates Secretory Cell Differentiation of the Human Airway Epithelium

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Abstract

Basal cells (BC) are the stem/progenitor cells of the human airway epithelium capable of differentiating into secretory and ciliated cells. Notch signaling activation increases BC differentiation into secretory cells, but the role of individual Notch ligands in regulating this process in the human airway epithelium is largely unknown. The objective of this study was to define the role of the Notch ligand JAG1 in regulating human BC differentiation. JAG1 over-expression in BC increased secretory cell differentiation, with no effect on ciliated cell differentiation. Conversely, knockdown of JAG1 decreased expression of secretory cell genes. These data demonstrate JAG1-mediated Notch signaling regulates differentiation of BC into secretory cells.

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Acknowledgments

We thank N. Mohamed for help in preparing this manuscript. These studies were supported, in part, by R01HL107882; R01HL107882-S; P20 HL113443, and R01HL1189541. KG was supported, in part by a NYSTEM Fellowship. Research reported in this publication was supported by NIH and the Family Smoking Prevention and Tobacco Control Act. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug Administration.

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Authors and Affiliations

  1. Department of Genetic Medicine, Weill Cornell Medical College, 1300 York Avenue, Box 164, New York, NY, 10065, USA

    Kazunori Gomi, Michelle R. Staudt, Jacqueline Salit, Robert J. Kaner, Jonna Heldrich, Allison M. Rogalski, Vanessa Arbelaez, Ronald G. Crystal & Matthew S. Walters

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  1. Kazunori Gomi
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Correspondence to Matthew S. Walters.

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The funders of this study had no role in the design and conduct of the study; not in the collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

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Gomi, K., Staudt, M.R., Salit, J. et al. JAG1-Mediated Notch Signaling Regulates Secretory Cell Differentiation of the Human Airway Epithelium. Stem Cell Rev and Rep 12, 454–463 (2016). https://doi.org/10.1007/s12015-016-9656-6

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