Pedone Elisa, Failli Mario, Gambardella Gennaro, De Cegli Rossella, La Regina Antonella, di Bernardo Diego, Marucci Lucia
Department of Engineering Mathematics, University of Bristol, Bristol BS8 1UB, UK.
School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
iScience. 2022 Jan 10;25(2):103756. doi: 10.1016/j.isci.2022.103756. eCollection 2022 Feb 18.
The Wnt/β-catenin pathway is involved in development, cancer, and embryonic stem cell (ESC) maintenance; its dual role in stem cell self-renewal and differentiation is still controversial. Here, by applying an system enabling inducible gene expression control, we report that moderate induction of transcriptionally active exogenous β-catenin in β-catenin null mouse ESCs promotes epiblast-like cell (EpiLC) derivation . Instead, in wild-type cells, moderate chemical pre-activation of the Wnt/β-catenin pathway promotes EpiLC derivation. Finally, we suggest that moderate β-catenin levels in β-catenin null mouse ESCs favor early stem cell commitment toward mesoderm if the exogenous protein is induced only in the "ground state" of pluripotency condition, or endoderm if the induction is maintained during the differentiation. Overall, our results confirm previous findings about the role of β-catenin in pluripotency and differentiation, while indicating a role for its doses in promoting specific differentiation programs.
Wnt/β-连环蛋白信号通路参与发育、癌症以及胚胎干细胞（ESC）的维持；其在干细胞自我更新和分化中的双重作用仍存在争议。在此，通过应用一种能够实现诱导性基因表达控制的系统，我们报告称，在β-连环蛋白缺失的小鼠胚胎干细胞中适度诱导转录活性外源性β-连环蛋白可促进类上胚层细胞（EpiLC）的产生。相反，在野生型细胞中，Wnt/β-连环蛋白信号通路的适度化学预激活可促进EpiLC的产生。最后，我们表明，如果仅在多能性状态的“基态”诱导外源性蛋白，β-连环蛋白缺失的小鼠胚胎干细胞中适度的β-连环蛋白水平有利于早期干细胞向中胚层定向分化；如果在分化过程中维持诱导，则有利于向内胚层分化。总体而言，我们的结果证实了先前关于β-连环蛋白在多能性和分化中作用的发现，同时表明其剂量在促进特定分化程序中发挥作用。
