February 12, 2010

Mouse Skin Cells Changed Directly into Nerve Cells

Image of red-labelled neurons Adding 3 genes to mouse skin cells prompted their conversion into these neurons within 12 days.Thomas Vierbuchen, Stanford University School of Medicine.

A trio of genes added to mouse skin cells can transform them directly into functioning nerve cells, a new study reports. With further research, this basic technique may lead to treatments for Alzheimer’s, Parkinson’s disease and other neurological disorders.

The new study builds on earlier research showing that adding just a few genes to fibroblasts, a type of skin cell, can convert them into versatile cells called induced pluripotent stem cells, or iPS cells. iPS cells share many characteristics of embryonic stem cells. Both can grow indefinitely in a laboratory dish, and both can theoretically change, or differentiate, into all cell types found in the body. But the process of creating iPS cells and then coaxing them into new cell types is time-consuming and inefficient. Typically, only about 1 or 2% of cells successfully adopt a new identity.

Dr. Marius Wernig and colleagues at Stanford University School of Medicine sought to bypass the iPS step and convert already-differentiated cells directly a new type. They were encouraged by the earlier success of an NIH-funded team at Harvard, who in 2008 used 3 genes to convert one type of pancreatic cell directly into another pancreatic cell that secretes insulin. The Stanford team set out to reprogram skin cells directly into nerve cells. Their research was supported in part by NIH’s National Institute of Neurological Disorders and Stroke (NINDS).

As described in the January 27, 2010, online edition of Nature, the scientists identified 19 genes known to be involved in either cellular reprogramming or neural development and function. The genes all code for transcription factors, proteins that bind to DNA and turn other genes on and off. The researchers inserted the genes into lentiviruses and added the viruses to fibroblast cells from embryonic mice. A month later, the cells had the appearance of nerve cells and were producing neural proteins.

The scientists further narrowed the 19 genes down to just 3 that could quickly and efficiently transform fibroblasts taken from either embryonic or young mice into nerve cells. About 20% of the fibroblasts converted into neural cells in less than a week. Tests showed that the newly transformed cells not only looked but also behaved like neurons. They formed functional connections, or synapses, with each other and with brain-derived neurons in a laboratory dish.

“We were very surprised by both the timing and the efficiency,” said Wernig. “This is much more straightforward than going through iPS cells, and it’s likely to be a very viable alternative.”

The technique can now be studied to learn more about how cellular identities are determined and how they can be manipulated. Wernig and his colleagues are attempting to make similar conversions with human cells. But they note that much more research is needed before this type of procedure could be considered for clinical use.

—by Vicki Contie

Related Links