News Brief: An Express Route From Fibroblasts to Neurons
If you want to study human neurons, where can you get them? One promising approach is reprogramming, where skin cells are converted into induced pluripotent stem (iPS) cells, which are then differentiated to neuronal cells. Last year, Marius Wernig and his colleagues at Stanford University School of Medicine in Palo Alto, California streamlined that strategy by skipping the iPS step and converting fibroblasts directly into neurons. That, however, was in mice. Today, Wernig’s group reports in Nature that they have created functioning neuronal cells directly from human postnatal fibroblasts. Their technique may simplify the production of patient-specific neurons, which have potential uses in in vitro disease modeling, drug screening, and regenerative medicine.
Using mouse cells, the researchers had shown that lentivirus-based expression of three transcription factors converted fibroblasts into neuronal cells (Vierbuchen et al., 2010; also see news story at the Alzheimer Research Forum). They now report that just one additional transcription factor, NeuroD1, is needed to create human induced neuronal (iN) cells with mature neuronal morphology, gene expression, and action potential firing.
When plated with mouse cortical neurons, the cells showed post-synaptic currents, indicating the presence of functional synapses. On other measures, however, the neurons appeared relatively immature, and more work will be needed to create fully differentiated neurons of various types.
Made-to-order neurons like these could offer powerful models for neurological disease, including a wide range of pain conditions, and serve as much-needed platforms for drug discovery. In a review in Neuron, also published today, Kevin Eggan and colleagues at Harvard University, Cambridge, Massachusetts describe results so far using neuronal cells generated from iPS cells. They highlight the pressing need for human neurons, because results in animal models are failing again and again to translate into humans—a situation well known to pain researchers.
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