Replacement Neurons
A simple genetic ­recipe reveals the surprising flexibility of adult cells

Source: “Direct conversion of fibroblasts to functional neurons by defined factors”
Marius Wernig et al.
Nature 463: 1035-1041

Results: By making a few simple genetic tweaks, scientists can transform mouse skin cells directly into brain cells, without first returning them to the embryonic state required by previous methods. The resulting cells express neuron-specific genes, have the characteristic branching shape of neurons, and form connections both with each other and with regular neurons collected from the brain.

Why it matters: The research could someday offer an effective way to replace damaged neurons. Because brain cells derived from a skin graft would be genetically identical to the patient’s own tissue, they wouldn’t carry the risk of immune rejection associated with transplants. And scientists say the technique is faster than the existing approach to generating replacement brain cells from an individual patient: reprogramming adult cells to behave like embryonic cells and then prodding them to develop into neurons.

Methods: Scientists began by studying the genes for 19 transcription factors–proteins that bind to DNA and regulate expression of other genes. All were known to play a role in neural development and were found only in the brain. When the researchers used viruses to deliver two genes known to be particularly important for neural development into skin cells growing in a dish, they discovered that one of them had the power to convert the cells into what looked like immature neurons. They identified two additional genes that made the process faster and more consistent.

Next steps: The researchers are trying to repeat the process with human cells. They also plan to transplant the reprogrammed mouse cells into the brains of engineered mice that have a disease similar to Parkinson’s. Those experiments could reveal whether the cells can function properly in the brain and relieve symptoms of the disease.