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 Juxtacrine Wnts select and maintain lung stem cells, and injury-induced autocrine Wnts recruit stem cells. 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.

中文翻译：

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单细胞 Wnt 信号壁龛维持肺泡 2 型细胞的干性

成纤维细胞作为肺干细胞生态位我们的每一次呼吸都会通过肺中称为肺泡的小囊为血液提供氧气。AT1 细胞排列在肺泡内并介导气体交换，而 AT2 细胞分泌肺表面活性剂。一部分 AT2 也可作为干细胞，在整个成年期缓慢产生新的肺泡细胞。纳巴恩等人。表明稀有的 AT2 干细胞在分泌 Wnt 的成纤维细胞旁边有一个特殊的生态位。这种 Wnt 活性是选择和维持干细胞所必需的。损伤通过在其他分泌表面活性剂的肺泡细胞中瞬时诱导自分泌 Wnt 来扩大干细胞库。这个简单但可扩展的生态位维持氧气输送，它被用于肺癌。科学，这个问题 p。1118 Juxtacrine Wnts 选择和维持肺干细胞，损伤诱导的自分泌 Wnts 募集干细胞。肺泡是肺的呼吸单位，是氧气进入血液的小囊。它们由介导气体交换的扁平肺泡 1 型 (AT1) 细胞和分泌表面活性剂的 AT2 细胞排列。罕见的 AT2 也可用作肺泡干细胞。我们发现 AT2 肺干细胞显示出活跃的 Wnt 信号，其中许多是接近单一的、表达 Wnt 的成纤维细胞。阻断 Wnt 分泌会消耗这些干细胞。离开 Wnt 生态位的子细胞转分化为 AT1：维持 Wnt 信号可防止转分化，而取消 Wnt 信号可促进转分化。损伤诱导 AT2 自分泌 Wnts，招募“大量”AT2s 作为祖细胞。因此，单个 AT2 干细胞位于单细胞成纤维细胞壁龛中，提供维持它们的近分泌 Wnt，而损伤诱导自分泌 Wnts 瞬时扩大祖细胞池。这个简单的生态位维持气体交换表面，并在癌症中被选中。