Lung Research Poster Session

Xin Wang, PhD

Research Fellow
Medicine
Allergy and Clinical Immunology
Authors
Xin Wang*, Nils Hallen, Sachin Samuchiwal, Minkyu Lee1, Katie Bucheit1, Neil Bhattacharyya, Soumya Raychaudhuri, Dan Dwyer, Tanya M. Laidlaw, Joshua A. Boyce, Maria Gutierrez-Arcelus, and Nora A. Barrett
Basal Cell Adhesion Molecule Marks An Airway Stem Cell Maintained Through IRS Signaling
Abstract

Recent studies in the human airway have identified transcriptionally distinct subsets of basal cells (BCs), but functional studies are lacking. Here we find two subsets of BCs in human and murine respiratory mucosa distinguished by expression of BC adhesion molecule (BCAM). Single cell RNA-sequencing, flow cytometry, ex-vivo cultures, and fate labelling experiments demonstrate that BCAM expression identifies airway stem cells among P63+KRT5+NGFR+ BCs. Accordingly, murine BCAMhi BCs were enriched in Wnt, Yap, and Rho signaling pathways and expressed higher levels of Trp63 than BCAMlo BCs. BCAMhi BCs are increased in the sinonasal mucosa of patients with chronic rhinosinusitis with nasal polyps (CRSwNP), a chronic inflammatory disease associated with type 2 (T2) cytokines. In cultured BCs, which express uniformly high levels of BCAM, expression of BCAM and TP63 was upregulated through an IL-4/13 and IRS-dependent signaling pathway that is increased in CRSwNP, as compared to CRS without nasal polyps (CRSsNP). These findings establish BCAM as a marker of airway stem cells and demonstrate that T2 inflammation promotes a stem state associated with augmented BCAM expression.