التفاصيل البيبلوغرافية
| العنوان: |
ΔN-Tp63 Mediates Wnt/β-Catenin-Induced Inhibition of Differentiation in Basal Stem Cells of Mucociliary Epithelia. |
| المؤلفون: |
Haas, Maximilian, Gómez Vázquez, José Luis, Sun, Dingyuan Iris, Tran, Hong Thi, Brislinger, Magdalena, Tasca, Alexia, Shomroni, Orr, Vleminckx, Kris, Walentek, Peter |
| المصدر: |
Cell Reports; Sep2019, Vol. 28 Issue 13, p3338-3338, 1p |
| مستخلص: |
Mucociliary epithelia provide a first line of defense against pathogens. Impaired regeneration and remodeling of mucociliary epithelia are associated with dysregulated Wnt/β-catenin signaling in chronic airway diseases, but underlying mechanisms remain elusive, and studies yield seemingly contradicting results. Employing the Xenopus mucociliary epidermis, the mouse airway, and human airway Basal cells, we characterize the evolutionarily conserved roles of Wnt/β-catenin signaling in vertebrates. In multiciliated cells, Wnt is required for cilia formation during differentiation. In Basal cells, Wnt prevents specification of epithelial cell types by activating ΔN-TP63 , a master transcription factor, which is necessary and sufficient to mediate the Wnt-induced inhibition of specification and is required to retain Basal cells during development. Chronic Wnt activation leads to remodeling and Basal cell hyperplasia, which are reversible in vivo and in vitro , suggesting Wnt inhibition as a treatment option in chronic lung diseases. Our work provides important insights into mucociliary signaling, development, and disease. • ΔN-TP63 is a master regulator of stemness versus differentiation in mucociliary cells • Wnt/β-catenin inhibits differentiation by upregulating ΔN-TP63 in basal stem cells • Wnt/ΔN-TP63-induced mucociliary remodeling is reversible in vivo and in vitro • The Xenopus epidermis provides a model to study basal stem cells in vivo Impaired (re-)generation of lung epithelia is associated with Wnt signaling changes in animals and human lung disease patients. Haas et al. demonstrate that ΔN-TP63 is a Wnt-regulated master transcription factor inhibiting (re-)generation of new epithelial cells from stem cells. These findings are equally important for understanding animal development and disease mechanisms. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
