The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Notch-Dependent Differentiation of Adult Airway Basal Stem Cells
Open accessAbstract
Summary The epithelium lining the airways of the adult human lung is composed of ciliated and secretory cells together with undifferentiated basal cells (BCs). The composition and organization of this epithelium is severely disrupted in many respiratory diseases. However, little is known about the mechanisms controlling airway homeostasis and repair after epithelial damage. Here, we exploit the mouse tracheobronchial epithelium, in which BCs function as resident stem cells, as a genetically tractable model of human small airways. Using a reporter allele we show that the low level of Notch signaling at steady state is greatly enhanced during repair and the generation of luminal progenitors. Loss-of-function experiments show that Notch signaling is required for the differentiation, but not self-renewal, of BCs. Moreover, sustained Notch activation in BCs promotes their luminal differentiation, primarily towards secretory lineages. We also provide evidence that this function of Notch signaling is conserved in BCs from human airways. Notch signaling is active in steady state airways and increased during repair Notch is required for differentiation, but not self-renewal, of airway basal cells Notch promotes luminal differentiation of mouse basal stem cells Our data suggest this mechanism is conserved in human basal cells
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“However, in progenitor basal cells of airway epithelium Notch signaling is required for differentiation but not cell renewal [214], perhaps explaining the role of abrogated Notch signaling in pathogenesis of lung SQCC.”
BackgroundBest, S. A., De Souza, D. P., Kersbergen, A., Policheni, A. N., Dayalan, S., Tull, D., Rathi, V., Gray, D. H., Ritchie, M. E., McConville, M. J., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.02.006 · Cited by 217
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Metadata
- Authors
- Rock, J. R., Gao, X., Xue, Y., Randell, S. H., Kong, Y.-Y., & Hogan, B. L. M.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 8
- Issue
- 6
- Pages
- 639-648
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2080037964
- Cited by
- 465
- References
- 1
- FWCI
- 11.17
- Type
- journal article
- Language
- en
- Open access
- bronze
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