PT  - JOURNAL ARTICLE
AU  - Mu He
AU  - Bing Wu
AU  - Daniel D. Le
AU  - Wenlei Ye
AU  - Adriane W. Sinclair
AU  - Valeria Padovano
AU  - Yuzhang Chen
AU  - Kexin Li
AU  - Rene Sit
AU  - Michelle Tan
AU  - Michael J. Caplan
AU  - Norma Neff
AU  - Yuh Nung Jan
AU  - Spyros Darmanis
AU  - Lily Y. Jan
TI  - Single Cell RNAseq Reveals A Critical Role of Chloride Channels in Airway Development
AID  - 10.1101/735969
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 735969
4099  - http://biorxiv.org/content/early/2019/08/15/735969.short
4100  - http://biorxiv.org/content/early/2019/08/15/735969.full
AB  - The conducting airway forms a protective mucosal barrier and is the primary target of airway disorders. To better understand how airway developmental programs are established to support air breathing and barrier functions, we constructed a single-cell atlas of the human and mouse developing trachea. In this study, we uncover hitherto unrecognized heterogeneity of cell states with distinct differentiation programs and immune features of the developing airway. In addition, we find ubiquitous expression of CFTR and ANO1/TMEM16A chloride channels in the embryonic airway epithelium. We show that genetic inactivation of TMEM16A leads to airway defects commonly seen in cystic fibrosis patients with deficient CFTR, alters the differentiation trajectory of airway basal progenitors, and results in mucus cell hyperplasia and aberrant epithelial antimicrobial expression. Together, our study illuminates conserved developmental features of the mammalian airway and implicates chloride homeostasis as a key player in regulating mucosal barrier formation and function relevant to early onset airway diseases.