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

TLDR

Alveoli contain AT1 cells for gas exchange and AT2 cells that secrete surfactant, a subset of which act as slow‑renewing stem cells, and fibroblasts provide a niche that supports these stem cells. Rare AT2 stem cells reside in a Wnt‑producing fibroblast niche that selects and maintains them, and injury expands the pool by inducing autocrine Wnts in other AT2s, thereby sustaining oxygen delivery and being co‑opted in lung cancer. Nabhan et al.

Abstract

Fibroblasts as lung stem cell niche Each breath that we take provides oxygen to the bloodstream via tiny sacs in the lung called alveoli. AT1 cells line the alveoli and mediate gas exchange, whereas AT2 cells secrete lung surfactant. A subset of AT2s also serve as stem cells that slowly generate new alveolar cells throughout adult life. Nabhan et al. show that the rare AT2 stem cells have a special niche next to a fibroblast secreting Wnts. This Wnt activity is needed to select and maintain the stem cells. Injury expands the stem cell pool by transiently inducing autocrine Wnts in other surfactant-secreting alveolar cells. This simple but expandable niche sustains oxygen delivery, and it is co-opted in lung cancer. Science , this issue p. 1118