Yap/Taz inhibit goblet cell fate to maintain lung epithelial homeostasis.
Cell Rep
; 36(2): 109347, 2021 07 13.
Article
in En
| MEDLINE
| ID: mdl-34260916
ABSTRACT
Proper lung function relies on the precise balance of specialized epithelial cells that coordinate to maintain homeostasis. Herein, we describe essential roles for the transcriptional regulators YAP/TAZ in maintaining lung epithelial homeostasis, reporting that conditional deletion of Yap and Wwtr1/Taz in the lung epithelium of adult mice results in severe defects, including alveolar disorganization and the development of airway mucin hypersecretion. Through in vivo lineage tracing and in vitro molecular experiments, we reveal that reduced YAP/TAZ activity promotes intrinsic goblet transdifferentiation of secretory airway epithelial cells. Global gene expression and chromatin immunoprecipitation sequencing (ChIP-seq) analyses suggest that YAP/TAZ act cooperatively with TEA domain (TEAD) transcription factors and the NuRD complex to suppress the goblet cell fate program, directly repressing the SPDEF gene. Collectively, our study identifies YAP/TAZ as critical factors in lung epithelial homeostasis and offers molecular insight into the mechanisms promoting goblet cell differentiation, which is a hallmark of many lung diseases.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Lineage
/
Goblet Cells
/
Adaptor Proteins, Signal Transducing
/
YAP-Signaling Proteins
/
Transcriptional Coactivator with PDZ-Binding Motif Proteins
/
Homeostasis
/
Lung
Type of study:
Prognostic_studies
Limits:
Adult
/
Animals
/
Humans
Language:
En
Journal:
Cell Rep
Year:
2021
Document type:
Article