Neuroepithelial bodies and terminal bronchioles are niches for distinctive club cells that repair the airways following acute notch inhibition.

Autor:	Lingamallu SM; Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore 560065, India; Manipal Academy of Higher Education (MAHE), Madhav Nagar, Manipal 576104, India., Deshpande A; Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore 560065, India; The University of Trans-Disciplinary Health Sciences and Technology (TDU), Yelahanka 560064, Bangalore, India., Joy N; Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore 560065, India; SASTRA Deemed University, Tirumalaisamudram, Thanjavur 613401, India., Ganeshan K; Immunology Discovery, Genentech Inc., South San Francisco, CA 94080, USA., Ray N; National Centre for Biological Sciences, Tata Institute for Fundamental Research, Bangalore 560065, India., Ladher RK; National Centre for Biological Sciences, Tata Institute for Fundamental Research, Bangalore 560065, India., Taketo MM; Colon Cancer Project, Kyoto University Hospital-iACT, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan., Lafkas D; Immunology, Infectious Diseases, and Ophthalmology (I2O) Discovery and Translational Area, Roche Innovation Center, Basel, Switzerland., Guha A; Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore 560065, India. Electronic address: arjung@instem.res.in.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Sep 24; Vol. 43 (9), pp. 114654. Date of Electronic Publication: 2024 Aug 24.
DOI:	10.1016/j.celrep.2024.114654
Abstrakt:	Lower airway club cells (CCs) serve the dual roles of a secretory cell and a stem cell. Here, we probe how the CC fate is regulated. We find that, in response to acute perturbation of Notch signaling, CCs adopt distinct fates. Although the vast majority transdifferentiate into multiciliated cells, a "variant" subpopulation (v-CCs), juxtaposed to neuroepithelial bodies (NEBs; 5%-10%) and located at bronchioalveolar duct junctions (>80%), does not. Instead, v-CCs transition into lineage-ambiguous states but can revert to a CC fate upon restoration of Notch signaling and repopulate the airways with CCs and multiciliated cells. The v-CC response to Notch inhibition is dependent on localized activation of β-catenin in v-CCs. We propose that the CC fate is stabilized by canonical Notch signaling, that airways are susceptible to perturbations to this pathway, and that NEBs/terminal bronchioles comprise niches that modulate CC plasticity via β-catenin activation to facilitate airway repair post Notch inhibition. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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