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Publication : Single-cell Wnt signaling niches maintain stemness of alveolar type 2 cells.

First Author  Nabhan AN Year  2018
Journal  Science Volume  359
Issue  6380 Pages  1118-1123
PubMed ID  29420258 Mgi Jnum  J:260760
Mgi Id  MGI:6149362 Doi  10.1126/science.aam6603
Citation  Nabhan AN, et al. (2018) Single-cell Wnt signaling niches maintain stemness of alveolar type 2 cells. Science 359(6380):1118-1123
abstractText  Alveoli, the lung''s respiratory units, are tiny sacs where oxygen enters the bloodstream. They are lined by flat alveolar type 1 (AT1) cells, which mediate gas exchange, and AT2 cells, which secrete surfactant. Rare AT2s also function as alveolar stem cells. We show that AT2 lung stem cells display active Wnt signaling, and many of them are near single, Wnt-expressing fibroblasts. Blocking Wnt secretion depletes these stem cells. Daughter cells leaving the Wnt niche transdifferentiate into AT1s: Maintaining Wnt signaling prevents transdifferentiation, whereas abrogating Wnt signaling promotes it. Injury induces AT2 autocrine Wnts, recruiting "bulk" AT2s as progenitors. Thus, individual AT2 stem cells reside in single-cell fibroblast niches providing juxtacrine Wnts that maintain them, whereas injury induces autocrine Wnts that transiently expand the progenitor pool. This simple niche maintains the gas exchange surface and is coopted in cancer.
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