干瘪的
Wnt信号通路
生物
细胞生物学
LRP5
干细胞
再生(生物学)
祖细胞
LRP6型
肺
受体
间质细胞
免疫学
癌症研究
信号转导
内科学
生物化学
医学
作者
Ahmad Nabhan,Joshua D. Webster,Arun P. Wiita,Levi L. Blazer,Christine Everrett,Céline Eidenschenk,Alexander Arlantico,Ira Fleming,Hans Brightbill,Paul J. Wolters,Zora Modrušan,Somasekar Seshagiri,Stéphane Angers,Sachdev S. Sidhu,Kim Newton,Joseph R. Arron,Vishva M. Dixit
出处
期刊:Cell
[Elsevier]
日期:2023-07-01
卷期号:186 (14): 2995-3012.e15
被引量:4
标识
DOI:10.1016/j.cell.2023.05.022
摘要
Wnt ligands oligomerize Frizzled (Fzd) and Lrp5/6 receptors to control the specification and activity of stem cells in many species. How Wnt signaling is selectively activated in different stem cell populations, often within the same organ, is not understood. In lung alveoli, we show that distinct Wnt receptors are expressed by epithelial (Fzd5/6), endothelial (Fzd4), and stromal (Fzd1) cells. Fzd5 is uniquely required for alveolar epithelial stem cell activity, whereas fibroblasts utilize distinct Fzd receptors. Using an expanded repertoire of Fzd-Lrp agonists, we could activate canonical Wnt signaling in alveolar epithelial stem cells via either Fzd5 or, unexpectedly, non-canonical Fzd6. A Fzd5 agonist (Fzd5ag) or Fzd6ag stimulated alveolar epithelial stem cell activity and promoted survival in mice after lung injury, but only Fzd6ag promoted an alveolar fate in airway-derived progenitors. Therefore, we identify a potential strategy for promoting regeneration without exacerbating fibrosis during lung injury.
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