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
Affiliations
Hongmei Mou
The Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, MA 02114, USA; Corresponding author
Ying Yang
Columbia Center for Human Development and Pulmonary Allergy & Critical Care Medicine, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA
Molly A. Riehs
Department of Pathology, Boston Children’s Hospital, MA 02115, USA
Juliana Barrios
The Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, MA 02114, USA
Manjunatha Shivaraju
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA
Adam L. Haber
Computational Biology and Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
Daniel T. Montoro
Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Kimberly Gilmore
Division of Neonatology and Newborn Medicine, Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA
Elisabeth A. Haas
Department of Research, Rady Children’s Hospital, San Diego, CA 92123, USA
Brankica Paunovic
San Diego County Office of the Medical Examiner, San Diego, CA 92123, USA
Jayaraj Rajagopal
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA
Sara O. Vargas
Department of Pathology, Boston Children’s Hospital, MA 02115, USA
Robin L. Haynes
Department of Pathology, Boston Children’s Hospital, MA 02115, USA
Alan Fine
Pulmonary Division, Boston University School of Medicine, Boston, MA 02118, USA
Wellington V. Cardoso
Columbia Center for Human Development and Pulmonary Allergy & Critical Care Medicine, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA
Xingbin Ai
Division of Neonatology and Newborn Medicine, Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA; Corresponding author
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.
