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A new technique to transform human stem cells into neurons is faster, more efficient and more reliable than existing methods, according to a study published 5 June in Neuron1.
The method will allow researchers to generate large populations of neurons derived from human blood or skin cells. These lab-made neurons can be used to test drug treatments, and to better understand the effect of certain mutations on brain function.
Over the past few years, researchers have explored a number of methods for generating human neurons in culture. One such method involves programming stem cell lines to become neurons.
Traditionally, scientists had to use embryonic stem cells taken from early-stage embryos. But researchers can now reprogram blood or skin cells so that they revert back into stem cells, called induced pluripotent stem (iPS) cells. This allows researchers to generate neurons from individuals with specific disorders, such as autism, schizophrenia or Rett syndrome.
In the next step, scientists bathe these stem cell lines in chemicals that force them to express certain genes, setting neuron development into motion. But this step can be slow, taking from three to six weeks. It is also unreliable: Even a single cell line may produce neurons that have different properties each time.
Another method, published in 2011, transforms skin cells directly into neurons, skipping the reprogramming step. But this method is inefficient and produces few functional neurons.
In the new study, researchers looked to optimize the steps to functional neurons. Although most studies have found that stem cells must express four genes to become neurons, the researchers in the new study identified a single one — neurogenin-2 (NGN2) — that would do the trick.
Stem cells expressing NGN2 turn into immature neurons in one week and mature neurons a week after that. Nearly all the surviving starting cells become neurons.
The researchers looked at the expression of 73 genes in 100 neurons derived from two different iPS cell lines and one embryonic stem cell line using the new technique. Each neuron has similar patterns of gene expression, suggesting that the method consistently generates the same type of neuron with similar properties.
These cells form active junctions, or synapses, showing that they can communicate with other neurons. When injected into the brains of newborn mice, the cells can integrate into live neuronal networks. This shows the technique generates fully functional, mature neurons, the researchers say.
1: Zhang Y. et al. Neuron 78, 785-798 (2013) PubMed