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Recipe for human neuron development

March 15, 2017

Allen Institute for Brain Science researchers have published a recipe for how to grow a class of human neurons from stem cells in a dish. The paper, published this month in the journal Neuron, provides a window into how a subset of neurons develop in the human brain and an enticing promise of the future therapeutic potential of this knowledge.

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Neurons that use the chemical GABA to communicate belong to a class of neurons whose role is to help control the flow of information in neural circuits. When GABAergic neurons do not properly develop or function, they have been shown to play a role in disorders including autism, schizophrenia and epilepsy.

Researchers at the Allen Institute for Brain Science set out to understand how and when this class of neurons develops in the brain. Most cells originate in one of a few select regions and then migrate to their final locations, responding to a significant number of genetic cues along the way that guide their development into healthy, mature cells.

“This is the first study to characterize the diverse gene expression changes that take place in these kinds of neurons as they grow and mature, and also the first to compare the results we get in the dish against actual tissue,” says Jennie Close, Ph.D., Scientist II at the Allen Institute for Brain Science and lead author on the paper.

Neurons encounter many genetic switches along their developmental path, but notably, many of the genes Close and her team identified as crucial to GABAergic neuron development have already been implicated as key players in neurodevelopmental and psychiatric disorders.

Comparing the gene expression results they obtained by growing cells in a dish against actual tissue—at single-cell resolution—provided further confidence that the genes they identified as developmental markers in the dish were accurate, because they were the same genes used by cells from actual tissue. The gene expression patterns also aligned with data in the Allen Developing Mouse Brain Atlas.

Beyond satisfying scientific curiosity about how these neurons come to be, understanding the process of GABAergic neuron development could also have exciting applications in medicine.

“Because of the location in which these neurons arise, being able to grow these cells could have tremendous therapeutic applications, including transplantation,” says Close. “Single-cell resolution is key, since being able to see gene expression at the level of individual cells will provide insight into how to develop effective protocols to generate specific populations that will someday be necessary for therapeutic transplants.”