TGFβ and Wnt Signaling Pathways Cooperatively Enhance Early Dopaminergic Differentiation of the Unrestricted Somatic Stem Cells.

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.