Airway basal stem cells generate distinct subpopulations of PNECs
| Autor: | Elisabeth A. Haas, Jayaraj Rajagopal, Brankica Paunovic, Sara O. Vargas, Alan Fine, Molly A. Riehs, Wellington V. Cardoso, Robin L. Haynes, Xingbin Ai, Juliana Barrios, Kimberly Gilmore, Adam L. Haber, Ying Yang, Daniel T. Montoro, Hongmei Mou, Manjunatha Shivaraju |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male BSC Basal (phylogenetics) Mice PNEC 0302 clinical medicine Influenza A Virus H1N1 Subtype Tubulin Basic Helix-Loop-Helix Transcription Factors Biology (General) Lung education.field_of_study Stem Cells Cell Differentiation Hyperplasia Cell biology Female Stem cell Sudden Infant Death Signal Transduction QH301-705.5 Population Neuropeptide Mice Transgenic Biology NP General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Neuroendocrine Cells Orthomyxoviridae Infections Immunity SIDS medicine Animals Humans Cell Lineage Progenitor cell education Tumor Suppressor Proteins NEB Neuropeptides Infant Epithelial Cells medicine.disease 030104 developmental biology Gene Expression Regulation NEHI 030217 neurology & neurosurgery Homeostasis Transcription Factors |
| Zdroj: | Cell reports Cell Reports, Vol 35, Iss 3, Pp 109011-(2021) |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY 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. In brief Mou et al. find that the conducting airway harbors three distinct types of pulmonary neuroendocrine cells, distinguished by gene expression, cell of origin, and existence in solitary and clustered configurations. The expansion of PNEC types is selectively associated with NEHI and SIDS, suggesting their contribution to disease. Graphical Abstract |
| Databáze: | OpenAIRE |
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