Skeletal myogenic potential of human and mouse neural stem cells

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Abstract

Distinct cell lineages established early in development are usually maintained throughout adulthood. Thus, adult stem cells have been thought to generate differentiated cells specific to the tissue in which they reside. This view has been challenged; for example, neural stem cells can generate cells that normally originate from a different germ layer. Here we show that acutely isolated and clonally derived neural stem cells from mice and humans could produce skeletal myotubes in vitro and in vivo, the latter following transplantation into adult animals. Myogenic conversion in vitro required direct exposure to myoblasts, and was blocked if neural cells were clustered. Thus, a community effect between neural cells may override such myogenic induction. We conclude that neural stem cells, which generate neurons, glia and blood cells, can also produce skeletal muscle cells, and can undergo various patterns of differentiation depending on exposure to appropriate epigenetic signals in mature tissues.

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Figure 1: Generation of myocytes/myotubes from clonally derived adult neural stem cells.
Figure 2: Inhibition of myogenic conversion in clustered ANSCs.
Figure 3: Clonally derived stem cells from adult mouse CNS differentiate in vivo into muscle fibers.
Figure 4: Human embryonic neural stem cells undergo myogenic conversion in vitro and in vivo.

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Acknowledgements

This work was supported by the EEC (Grants QLRT000894, QLRT-1999-31471), the Italian Telethon Foundation, the Spinal Cord Society (MN) (A.L.V.) and the Fondazione Pasteur-Cenci Bolognetti (G.C.). We thank Don Ward for help with the English.

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Correspondence to Giulio Cossu or Angelo L. Vescovi.

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