Cell Reports (Apr 2021)

Airway basal stem cells generate distinct subpopulations of PNECs

  • Hongmei Mou,
  • Ying Yang,
  • Molly A. Riehs,
  • Juliana Barrios,
  • Manjunatha Shivaraju,
  • Adam L. Haber,
  • Daniel T. Montoro,
  • Kimberly Gilmore,
  • Elisabeth A. Haas,
  • Brankica Paunovic,
  • Jayaraj Rajagopal,
  • Sara O. Vargas,
  • Robin L. Haynes,
  • Alan Fine,
  • Wellington V. Cardoso,
  • Xingbin Ai

Journal volume & issue
Vol. 35, no. 3
p. 109011

Abstract

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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.

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