Distinct cell lineages established early in development are usually maintai
ned throughout adulthood. Thus, adult stem cells have been thought to gener
ate 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 acu
tely isolated and clonally derived neural stem cells from mice and humans c
ould produce skeletal myotubes in vitro and in vivo, the latter following t
ransplantation into adult animals. Myogenic conversion in vitro required di
rect exposure to myoblasts, and was blocked if neural cells were clustered.
Thus, a community effect between neural cells may override such myogenic i
nduction. We conclude that neural stem cells, which generate neurons, glia
and blood cells, can also produce skeletal muscle cells, and can undergo va
rious patterns of differentiation depending on exposure to appropriate epig
enetic signals in mature tissues.