Single-cell Wnt signaling niches maintain stemness of alveolar type 2 cells
- PMID: 29420258
- PMCID: PMC5997265
- DOI: 10.1126/science.aam6603
Single-cell Wnt signaling niches maintain stemness of alveolar type 2 cells
Abstract
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.
Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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Comment in
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New insights and therapeutic targets: Lung injury and disease.J Thorac Cardiovasc Surg. 2019 Jan;157(1):416-420. doi: 10.1016/j.jtcvs.2018.09.026. Epub 2018 Oct 6. J Thorac Cardiovasc Surg. 2019. PMID: 30557958 No abstract available.
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