Scientists in the School of Medicine transformed mature liver cells from mice into functional neurons with the introduction of three new genes, marking the first time researchers anywhere have been able to “leapfrog from one fundamentally different tissue type to another,” according to a School of Medicine statement.

This same group of researchers, led by assistant professor of pathology and senior author Marius Wernig, showed in 2009 that it was possible to transform mice skin cells into neurons. The difference is that this new transformation occurs without first having to make the cells “pluripotent”–that is, without first inducing the potential to differentiate via the forced expression of certain genes. Previously, this was thought to be a necessary step.

“These liver cells unambiguously cross tissue-type boundaries to become fully functional neural cells,” Wernig said in a statment. “Even more surprising, these cells also simultaneously silence their liver-gene expression profile. They are not hybrids; they are completely switching their identities.”

Researchers transformed the liver cells, known as hepatocytes, by inserting via a virus three genes: Brn2, Ascl1 and Myt1l. Within two weeks, cells began to take on neural identities and suppress previous characteristics.

Wernig, along with postdoctoral scholar and first author Samuele Marro, built on a technique developed by professor of applied physics Stephen Quake. They analyzed the original and transformed liver cells to show that their product behaves like a true neuron and shuts down all gene expression associated with its previous function.

There is future potential for research on the application of these cells–for example, in whether they can be used to learn more about disease or in treatment. According to the press release, these cells could also help illuminate the process of cell differentiation.

“This is fascinating,” Wernig said. “We can imagine ways that the three introduced factors could stimulate neural gene expression, but how do they also down-regulate two completely unrelated donor networks–those of skin and liver cells?”

The research was funded jointly by the New York Stern Cell Foundation, the Stinehart/Reed Foundation, the Ellison Medical Foundation, the Howard Hughes Medical Institute and the National Institutes of Health.

–Ellora Israni