So far no evidence is available as to whether TGFβ and Wnt signaling pathways cooperatively modulate dopaminergic differentiation of the adult stem cells. To investigate the interaction between the two pathways in early dopaminergic differentiation, we cultured the newly introduced unrestricted somatic stem cells (USSCs) in neuron differentiation media followed by treatments with inducers and inhibitors of Wnt and TGF beta pathways either alone or in combinations. Our results showed that the level of Nurr-1 as a marker for dopaminergic neuron precursors and that of the nuclear β-catenin as the key effector of the active Wnt pathway were significantly elevated following the treatment with either TGFβ or BIO (the Wnt pathway inducer). Conversely, Nurr-1 expression was significantly reduced following the combined treatments with SB431542 (the TGFβ inhibitor) plus BIO or with TGFβ plus Dkk1 (the specific Wnt inhibitor). Nuclear β-catenin was also significantly reduced following combined treatments with SB431542 plus either BIO or TGFβ. Altogether, our results imply that Wnt and TGFβ signaling pathways cooperatively ensure the early dopaminergic differentiation of the USSC adult stem cells.

中文翻译：

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TGFβ和Wnt信号通路可协同增强不受限制的体干细胞的早期多巴胺能分化。

迄今为止，关于TGFβ和Wnt信号通路是否协同调节成年干细胞的多巴胺能分化，尚无证据。为了研究早期多巴胺能分化中这两种途径之间的相互作用，我们在神经元分化培养基中培养了新近引入的非限制性体细胞干细胞（USSCs），然后单独或组合使用Wnt和TGFβ途径的诱导剂和抑制剂进行治疗。我们的研究结果表明，在用TGFβ或BIO（Wnt途径诱导剂）治疗后，作为多巴胺能神经元前体标志物的Nurr-1水平和作为活性Wnt途径关键效应物的核β-catenin的水平均显着升高。 ）。反过来，用SB431542（TGFβ抑制剂）加BIO或TGFβ加Dkk1（特异性Wnt​​抑制剂）联合治疗后，Nurr-1表达显着降低。SB431542加BIO或TGFβ联合治疗后，β-catenin核也显着减少。总之，我们的结果暗示Wnt和TGFβ信号通路可协同确保USSC成体干细胞的早期多巴胺能分化。