Abstract
SUMMARYPulmonary 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.
Highlights
Pulmonary neuroendocrine cells (PNECs) comprise a rare population of epithelial cells in mammalian airways that uniquely express bioactive amines and neuropeptides (NPs), including calcitonin gene-related peptide (CGRP), gastrin-releasing peptide (GRP), and chromogranin A (CHGA) (Gosney et al, 1988; Weichselbaum et al, 2005)
TUBB3 analysis reveals three distinct types of PNECs in human airways During an analysis of neural innervation of human airways, we discovered rare cells in the airway epithelium expressing TUBB3, a neuron-specific tubulin beta 3 class III (TUBB3) (Figure 1A)
TUBB3 mostly overlapped with PNEC markers, including GRP, CHGA, synaptic vesicle glycoprotein 2A (SV2), and PGP9.5 (Figures 1B and S1B)
Summary
Pulmonary neuroendocrine cells (PNECs) comprise a rare population of epithelial cells in mammalian airways that uniquely express bioactive amines and neuropeptides (NPs), including calcitonin gene-related peptide (CGRP), gastrin-releasing peptide (GRP), and chromogranin A (CHGA) (Gosney et al, 1988; Weichselbaum et al, 2005). These cells are crucial components of the innate immunity in airways, responding to environmental stimuli by releasing NPs and neurotransmitters to mediate a variety of functions. NEBs and the total number of PNECs are markedly increased in a variety of human diseases, such as neuroendocrine hyperplasia in infancy (NEHI) (Young et al, 2011), asthma (Sui et al, 2018), and sudden infant death syndrome (SIDS) (Cutz et al, 1996, 2007)
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