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Scientists Grow Miniature Brains From Skin Cells Of Autistic Patients

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Caroline Reid

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clockJul 17 2015, 19:48 UTC
1180 Scientists Grow Miniature Brains From Skin Cells Of Autistic Patients
This is a human brain organoid showing complex internal organization, with immature proliferating cells (red) and a surrounding layer of maturing neurons (green). Jessica Mariani.

Due to their complexity, and the fact that brain development is difficult to emulate in the lab, scientists struggle to understand neurological disorders such as autism and schizophrenia. In a bid to overcome these hurdles, a group of researchers has been growing mini brains in petri dishes from the skin cells of autistic patients. The micro-brains might not be big, but what they have shown the researchers may have big implications for the future of autism research. 

Generally, studies into autism examine patient genomes and search for any mutations that might be responsible for the disorder. Then, once a possible mutation is identified, its effects on development are tested on animal models or cells. The research team, however, decided to take the opposite approach: grow a brain and see which genes express themselves unusually. 

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"Instead of starting from genetics, we've started with the biology of the disorder itself to try to get a window into the genome," commented senior author Flora Vaccarino from the Yale School of Medicine. Her team's findings were published in Cell.

The researchers took a sample of skin cells from autistic patients as well as their unaffected fathers. This meant that scientists could compare how the genetically similar cells grow.

The researchers converted these skin cells into pluripotent stem cells. This type of cell is a sort of 'master cell' that can potentially become any other type of cell: brain cells, liver cells, lung cells, anything. In this experiment, the researchers grew the pluripotent cells into miniature brains. 

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The final "brain organoid" was only a few millimeters in diameter, nothing like the size of a fully developed human brain, but it was enough to see how early human brains grow differently. Those grown from the cells of autistic patients expressed some interesting differences during early growth phases compared with non-autistic cells.

The neural development, or the process that generates the brain and nervous system, was altered in the cells from autistic patients. The genes that were found to display different expression levels were those responsible for regulating neuronal development. Consequently, the brains produced too many inhibitory neurons. Inhibitory neurons are the cells in the brain that slow down and stop information eternally shooting around the brain – like traffic lights keeping traffic on the roads in check. 

An overproduction of these inhibitory neurons alongside the normal production of other neurons caused an imbalance in neuron types within the brain organoid. If we return to our road analogy, it means that this brain had too many traffic lights and the traffic (thoughts) was slowed down or stopped more often than in a neurotypical brain. 

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Intriguingly, the scientists located a single gene whose expression was abnormally strong in autistic brains and not as intensely expressed in neurotypical brains. When the expression of the single gene was suppressed, the autistic brain organoid did not have an imbalance of neuron types. This result suggests that there may be a way of restoring the neuronal balance in autistic patients. 

It is important to note that this research is still strictly confined to petri dishes. However, Vaccarino thinks that this research may one day lead to new treatments for autism. She said: "This study speaks to the importance of using human cells and using them in an assay that could bring a better understanding of the pathophysiology of autism and with that, possibly better treatments." 


  • tag
  • brain,

  • autism,

  • cells

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