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Rony Chidiac¹, Andy Yang², Elli Kubarakos²

¹Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.

Stem cell reports

|January 17, 2025

概括

Wnt信号受体Frizzled 2 (FZD2) 和Frizzled 7 (FZD7) 在人类多能干细胞 (hPSC) 中的中皮细胞特异性中发挥着不同的作用. 它们的激活会影响Wnt-β-catenin信号传递,指导细胞在分化过程中的命运决策.

科学领域:

发育生物学发展生物学
干细胞生物学干细胞生物学
分子信号传输的方法

背景情况:

在胃流动过程中,Wnt-β-catenin信号传递对中皮特异性至关重要.
个别Wnt受体,特别是Frizzled (FZD) 蛋白质在指导中皮细胞类型中的确切作用尚不清楚.
了解Wnt受体的功能是控制人类多能干细胞 (hPSC) 差异化的关键.

研究的目的:

为了研究Frizzled 2 (FZD2) 和Frizzled 7 (FZD7) 受体在hPSCs的定向中皮分化的特定功能.
阐明FZD2和FZD7的激活动力学如何差异调节Wnt-β-catenin信号传递和随后的中皮模式.
确定FZD2和FZD7是否在指定对轴与侧面半皮方面具有非冗余的作用.

主要方法:

利用基于抗体的激素来选择性地激活hPSC上的Frizzled (FZD) 和LRP5/6受体.
在hPSC膜上量化FZD2和FZD7受体表达.
在FZD受体刺激后分析了β-catenin信号激活的动力学.
评估了FZD2和FZD7激活对对轴心和侧面半皮分化结果的影响.

主要成果:

FZD2和FZD7受体在hPSCs的表面表达.
激活FZD7增强了双向和侧向间皮分化.
激活FZD2优选促进了对轴性介质体的分化,同时抑制了侧面介质体.
FZD2的激活导致了持续的Wnt-β-catenin信号发送,而FZD7的激活导致了短暂的信号发送,影响了谱系选择.

结论:

在hPSC衍生的中皮特征中,FZD2和FZD7表现出不同的,非冗余的功能.
FZD2和FZD7的差异激活动力学调节Wnt-β-catenin信号传递,以控制中皮层谱系分支.
针对特定的FZD受体提供了一种精确控制hPSCs定向分化到特定中皮亚型的策略.

关键词:

发的受体受体.没有Wnt激动剂.没有信号发送.有针对性的差异化.人类多能干细胞干细胞介质皮层的规格规范.

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