Partial induction of the myogenic program in noncommitted adult stem cells

The ability of multipotent adult stem cells (MASCs) and mesenchymal stem cells (MSCs) to acquire certain biochemical and functional properties of differentiated cells in response to various inductive cues has raised hopes to utilize such cells for therapeutic purposes. It is of particular importance to define precisely the differentiation status of induced MASCs and MSCs, and to determine the signaling pathways that control their differentiation. The identification of such signals might help to expand and enhance specific differentiation pathways to allow the formation of fully functional muscle cells from undetermined stem cells. Here, we have analyzed the ability of MASCs to contribute to the formation of muscle syncytia. We also investigated the intracellular signaling cascades that were initiated by Wnt molecules in a murine bone marrow-derived MASC population. We found that the partial recapitulation of the myogenic program depends on Wnt-mediated signaling via beta-catenin and protein kinase C, but not protein kinase A (PKA). Our experiments indicate that Wnt-mediated signaling via beta-catenin and protein kinase C (PKC) does not suffice to promote cell-autonomous differentiation of MASCs, but leads to acquisition of some properties of muscle cells that allow Wnt-induced cells to fuse to preexisting myotubes.