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Studies Show Improvements in Direct Skin Cell to Neurons Conversion



Ten days later a second team of Stanford researchers, this time in the lab of Gerald Crabtree, published a Nature online report demonstrating how they had improved on Wernig's method and greatly increased the efficiency of converting skin to neuron. Wernig's team converted the cells using a combination of four particular proteins as transcription factors, with a modest 2 to 4 percent efficiency. In addition, the cells produced showed limited electrical signaling ability. Crabtree's group began with two microRNAs known to be involved in the maturation of neural stem cells.

Alone, the microRNAs also showed a modest yield of 2 to 3 percent neurons, but they generated the electrical signals that neurons use to communicate with one another and they budded off synaptic vesicles, just as adult neurons ordinarily do. The team then added two of the factors used in Wernig's study and the yield jumped dramatically to 20 percent, while also maintaining improved electrical functionality.

Asa Abeliovich and his team at Columbia University (New York, USA) then weighed in on the subject with a paper published in the August 5 issue of Cell Vol. 146(3) in which they reported using a different mix of genetic factors and culture conditions to create forebrain neurons from the skin of both normal individuals and those with familial, early onset Alzheimer's. In both cases the cells matured and behaved like neurons responding to neurotransmitters. The cells derived from patients were also clearly abnormal. They had altered ability to process and transport the amyloid precursor protein (APP) and a resulting increase in production of amyloid beta, which has long been a suspect in the disease.

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— Compiled from CIRM President's Science Update and from Stanford University press releases