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新型Wnt替代蛋白可促进类器官生长
2020-08-23 15:31
来源：小柯机器人

美国斯坦福大学医学院K. Christopher Garcia团队开发出下一代Wnt替代品，可支持类器官生长。相关论文于2020年8月19日在线发表于《细胞—干细胞》。

研究人员设计和工程化了水溶性且Fzd亚型特异性的“下一代替代品”（NGS）Wnt，其可与Fzd和Lrp6异源二聚体。NGS Wnt支持长期扩增多种不同类型的类器官，包括肾脏、结肠、肝细胞、卵巢和乳房。NGS Wnts在类器官扩增和单细胞类器官生长方面优于Wnt3a条件培养基。
 
Fzd亚型特异性NGS Wnt的体内给药表明，Fzd5和/或Fzd8受体的激动作用可以促进成人肠道隐窝的增殖，而广谱的Fzd受体则可以诱导肝区形成。
 
因此，NGS Wnt提供了一个统一的类器官扩增方案以及一个实验室“工具箱”，可用于剖析Fzd亚型在干细胞生物学中的功能。
 
据介绍，由于Wnt信号在干细胞动态平衡中的基本功能，其在再生医学中的潜力尚未开发。但是，Wnt脂化和Wnt-Fzd交叉反应已阻碍了Wnt的转化应用。
 
附：英文原文

Title: Next-Generation Surrogate Wnts Support Organoid Growth and Deconvolute Frizzled Pleiotropy In Vivo

Author: Yi Miao, Andrew Ha, Wim de Lau, Kanako Yuki, António J.M. Santos, Changjiang You, Maarten H. Geurts, Jens Puschhof, Cayetano Pleguezuelos-Manzano, Weng Chuan Peng, Ramazan Senlice, Carol Piani, Jan W. Buikema, Oghenekevwe M. Gbenedio, Mario Vallon, Jenny Yuan, Sanne de Haan, Wieger Hemrika, Kathrin Rsch, Luke T. Dang, David Baker, Melanie Ott, Philippe Depeille, Sean M. Wu, Jarno Drost, Roeland Nusse, Jeroen P. Roose, Jacob Piehler, Sylvia F. Boj, Claudia Y. Janda, Hans Clevers, Calvin J. Kuo, K. Christopher Garcia

Issue&Volume: 2020-08-19

Abstract: Modulation of Wnt signaling has untapped potential in regenerative medicine due toits essential functions in stem cell homeostasis. However, Wnt lipidation and Wnt-Frizzled(Fzd) cross-reactivity have hindered translational Wnt applications. Here, we designedand engineered water-soluble, Fzd subtype-specific “next-generation surrogate” (NGS)Wnts that hetero-dimerize Fzd and Lrp6. NGS Wnt supports long-term expansion of multipledifferent types of organoids, including kidney, colon, hepatocyte, ovarian, and breast.NGS Wnts are superior to Wnt3a conditioned media in organoid expansion and single-cellorganoid outgrowth. Administration of Fzd subtype-specific NGS Wnt in vivo reveals that adult intestinal crypt proliferation can be promoted by agonism of Fzd5and/or Fzd8 receptors, while a broad spectrum of Fzd receptors can induce liver zonation.Thus, NGS Wnts offer a unified organoid expansion protocol and a laboratory “toolkit” for dissecting the functions of Fzd subtypes in stem cell biology.

DOI: 10.1016/j.stem.2020.07.020

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30358-1

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
官方网址：https://www.cell.com/cell-stem-cell/home
投稿链接：https://www.editorialmanager.com/cell-stem-cell/default.aspx


本期文章：《细胞—干细胞》：Online/在线发表

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