小柯机器人

美国基因泰克公司Vishva M. Dixit等研究人员合作利用Frizzled特异性激动剂进行靶向的肺泡再生。2023年6月14日，《细胞》杂志在线发表了这项成果。

在肺泡中，研究人员显示不同的Wnt受体由上皮细胞（Fzd5/6）、内皮细胞（Fzd4）和基质细胞（Fzd1）表达。Fzd5是肺泡上皮干细胞活动的唯一需要，而成纤维细胞则利用不同的Fzd受体。使用扩大的Fzd-Lrp激动剂，研究人员可以通过Fzd5或意外的非经典Fzd6激活肺泡上皮干细胞的经典Wnt信号。Fzd5激动剂（Fzd5^ag）或Fzd6^ag刺激了肺泡上皮干细胞的活性，促进了小鼠肺部损伤后的存活，但只有Fzd6^ag促进了气道源性祖细胞的肺泡命运。因此，研究人员确定了一个潜在的策略，可在肺部损伤期间促进再生而不加剧纤维化。

据了解，Wnt配体使Frizzled（Fzd）和Lrp5/6受体寡聚，从而控制许多物种中干细胞的特化和活动。Wnt信号如何在不同的干细胞群中被选择性地激活，而且还往往是在同一器官内，目前还不清楚。

附：英文原文

Title: Targeted alveolar regeneration with Frizzled-specific agonists

Author: Ahmad N. Nabhan, Joshua D. Webster, Jarret J. Adams, Levi Blazer, Christine Everrett, Celine Eidenschenk, Alexander Arlantico, Isabel Fleming, Hans D. Brightbill, Paul J. Wolters, Zora Modrusan, Somesekar Seshagiri, Stephane Angers, Sachdev S. Sidhu, Kim Newton, Joseph R. Arron, Vishva M. Dixit

Issue&Volume: 2023-06-14

Abstract: 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.

DOI: 10.1016/j.cell.2023.05.022

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00541-X