At the time, Majumder wanted to know what would happen if those particular genes ” the last to be activated were turned on first, by-passing the normal development process. So he and his colleagues created a new gene (REST-VP16) that was modeled on the natural repressor gene, but actually worked to turn the genes on. We converted what is normally a brake into a gas pedal, he says.

So now the researchers tested what would happen when myoblasts, which are normally committed to become muscle, were genetically altered to express the new gas pedal gene attached to a molecular switch. To his delight, the experiment worked.  When REST-VP16 was turned on in myoblasts, it was enough to block the cells ™ entry into the muscle differentiation pathway and caused them to show neuronal properties.

If you keep the REST-VP16 gene off, the myoblasts became muscle, he says. If you turn the gene on, the cells didn ™t even enter the muscle differentiation pathway. Instead, they looked like neurons, turned a large number of neuronal genes on and showed physiological activities of neurons. 

 The study not only suggests that the fate of stem cells can potentially be altered, says Majumder, but provides an experimental way of driving those changes.

Working with Majumder were M. D. Anderson researchers Yumi Watanabe, Ph.D., Sei Kameoka, Vidya Gopalakrishnan, Ph.D., Kenneth Aldape, M.D.,  Zhizhong Pan, Ph.D., and Frederick Lang, M.D.  The study was supported by grants from the National Cancer Institute. Watanabe is now at Kyoto University and Kameoka is at Harvard University.