Cell reports (Cambridge), 2021-07, Vol.36 (2), p.109347-109347, Article 109347
2021
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- Autor(en) / Beteiligte
- Titel
- Yap/Taz inhibit goblet cell fate to maintain lung epithelial homeostasis
- Ist Teil von
- Cell reports (Cambridge), 2021-07, Vol.36 (2), p.109347-109347, Article 109347
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. [Display omitted] •YAP/TAZ maintain alveolar and airway integrity in adult mice•Nuclear YAP/TAZ restrict goblet cell differentiation and mucin hypersecretion•YAP/TAZ, TEAD, and the NuRD complex cooperate to repress SPDEF expression•Hippo-regulated YAP/TAZ intersect with goblet cell-specifying cytokine cues Hicks-Berthet et al. report that deletion of YAP/TAZ in adult lung epithelium results in defects that include widespread goblet cell metaplasia. YAP/TAZ restrict goblet cell differentiation through a transcriptional network that includes direct SPDEF repression. These findings offer insight into signals that direct goblet cell fate in the lung.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2211-1247eISSN: 2211-1247DOI: 10.1016/j.celrep.2021.109347Titel-ID: cdi_doaj_primary_oai_doaj_org_article_51d769715d5644f496c2be0ccf9745a0
- Format
- –
- Schlagworte
- Adaptor Proteins, Signal Transducing - metabolism, Adult, Animals, Cell Lineage, Cells, Cultured, Cytokines - metabolism, Gene Expression Profiling, Gene Expression Regulation, goblet cell, Goblet Cells - cytology, Goblet Cells - metabolism, Hippo, Hippo Signaling Pathway, Homeostasis, Humans, lung, Lung - cytology, Metaplasia, Mice, Mice, Knockout, Mucin, Mucin 5AC - metabolism, NuRD, Promoter Regions, Genetic - genetics, Proto-Oncogene Proteins c-ets - genetics, Proto-Oncogene Proteins c-ets - metabolism, Spdef, Taz, TEA Domain Transcription Factors - metabolism, Tead, Transcriptional Coactivator with PDZ-Binding Motif Proteins - metabolism, Yap, YAP-Signaling Proteins