1. Airway basal stem cells generate distinct subpopulations of PNECs.
- Author
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Mou H, Yang Y, Riehs MA, Barrios J, Shivaraju M, Haber AL, Montoro DT, Gilmore K, Haas EA, Paunovic B, Rajagopal J, Vargas SO, Haynes RL, Fine A, Cardoso WV, and Ai X
- Subjects
- Animals, Basic Helix-Loop-Helix Transcription Factors genetics, Basic Helix-Loop-Helix Transcription Factors metabolism, Cell Differentiation, Epithelial Cells classification, Epithelial Cells metabolism, Female, Gene Expression Regulation, Humans, Hyperplasia genetics, Hyperplasia metabolism, Hyperplasia pathology, Infant, Influenza A Virus, H1N1 Subtype growth & development, Influenza A Virus, H1N1 Subtype pathogenicity, Lung, Male, Mice, Mice, Transgenic, Neuroendocrine Cells classification, Neuroendocrine Cells metabolism, Neuropeptides genetics, Neuropeptides metabolism, Orthomyxoviridae Infections genetics, Orthomyxoviridae Infections metabolism, Orthomyxoviridae Infections pathology, Orthomyxoviridae Infections virology, Signal Transduction, Stem Cells classification, Stem Cells metabolism, Sudden Infant Death genetics, Sudden Infant Death pathology, Transcription Factors genetics, Transcription Factors metabolism, Tubulin metabolism, Tumor Suppressor Proteins genetics, Tumor Suppressor Proteins metabolism, Cell Lineage genetics, Epithelial Cells pathology, Neuroendocrine Cells pathology, Stem Cells pathology, Tubulin genetics
- Abstract
Pulmonary neuroendocrine cells (PNECs) have crucial roles in airway physiology and immunity by producing bioactive amines and neuropeptides (NPs). A variety of human diseases exhibit PNEC hyperplasia. Given accumulated evidence that PNECs represent a heterogenous population of cells, we investigate how PNECs differ, whether the heterogeneity is similarly present in mouse and human cells, and whether specific disease involves discrete PNECs. Herein, we identify three distinct types of PNECs in human and mouse airways based on single and double positivity for TUBB3 and the established NP markers. We show that the three PNEC types exhibit significant differences in NP expression, homeostatic turnover, and response to injury and disease. We provide evidence that these differences parallel their distinct cell of origin from basal stem cells (BSCs) or other airway epithelial progenitors., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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