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May 15 2013

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Turning Stem Cells into Brain Cells Sheds Light on Neural Development

stem cellsStem cells have the unique ability to develop, or differentiate, into other kinds of cells in the body. Researchers have now manipulated human stem cells so that they produce the types of brain cells that play important roles in neurodevelopmental disorders such as epilepsy, schizophrenia, and autism.

This new model cell system will allow neuroscientists to investigate normal brain development, as well as to identify specific disruptions in biological signals that may contribute to neuropsychiatric diseases.

The research, conducted by scientists from The Children’s Hospital of Philadelphia and Memorial Sloan-Kettering Cancer Center, harnesses human embryonic stem cells, which differentiate into a broad range of different cell types. The investigators directed the stem cells into becoming cortical interneurons — a class of brain cells that, by releasing the neurotransmitter GABA, controls electrical firing in brain circuits.

“Interneurons act like an orchestra conductor, directing other excitatory brain cells to fire in synchrony,” said study co-leader Stewart A. Anderson, MD, a research psychiatrist at Children’s Hospital. “However, when interneurons malfunction, the synchrony is disrupted, and seizures or mental disorders can result.”

Dr. Anderson and his study co-leader Lorenz Studer, MD, of the Center for Stem Cell Biology at Sloan-Kettering, derived interneurons in a laboratory model that simulates how neurons normally develop in the human forebrain.

stem cells“Unlike, say, liver diseases, in which researchers can biopsy a section of a patient’s liver, neuroscientists cannot biopsy a living patient’s brain tissue,” said Dr. Anderson.

It is therefore important to produce a cell culture model of brain tissue for studying neurological diseases, he added. Significantly, the human-derived cells in the current study also “wire up” in circuits with other types of brain cells taken from mice, when cultured together. Those interactions, Dr. Anderson said, allowed the study team to observe cell-to-cell signaling that occurs during forebrain development.

Dr. Anderson and his colleagues are using their cell model to better define molecular events that occur during brain development. By selectively manipulating genes in the interneurons, they hope to better understand how gene abnormalities may disrupt brain circuitry and give rise to particular diseases.

Those studies could ultimately help inform drug development by identifying molecules that could offer therapeutic targets for more effective treatments of neuropsychiatric diseases.

 

Permanent link to this article: http://www.research.chop.edu/blog/turning-stem-cells-into-brain-cells-sheds-light-on-neural-development/

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