Lab-Grown Brain Clumps Shed Light on Causes of Autism

Organoids prove revolutionary when used in autism research. Made of stem cells, which are undifferentiated cells that can specialize into various kinds of cells, organoids resemble tiny brains, like those of human embryos. These lab-grown organ buds are very new and developing quickly; in 2013, The Scientist called organoids one of the biggest advances in science. Just last week, the very first study using organoids to investigate the causes of autism was published.

Flora Vaccarino, a professor of child psychiatry and neurobiology at Yale University, led the study with the aim of identifying whether autism is the outcome of abnormal brain development. The researchers made stem cells from the skin cells collected from autistic patients with enlarged heads, a characteristic that exists in about 20% of autistic people. They made stem cells from the skin of the patients’ fathers who do not have autism spectrum disorder as their control group. Next, they manipulated the stem cells to develop into an assortment of forebrain neuronal cells. These became organoids. 

To verify that the organoids produced necessary components found in fetal brains, genetic sequencing and physiological tests were conducted on the organoids. When comparing the organoids derived from the patient’s cells with those from their fathers’, three major observations were made.

First, the genes contributing to the proliferation of cells were over-expressed in the autistic organoids as compared to in the non-autistic organoids. Second, an imbalance in the number of two types of neurons that are usually the same in quantity was identified. Third, gene expression data indicated a particular gene crucial for early brain development was over expressed in the autistic organoids. By engineering the DNA from the autistic organoids to reduce the over-expression of that particular gene, an incredible challenge was accomplished: the scientists successfully transformed cells from the autistic patients into organoids that lacked the neuronal imbalance.                 

Such research would be unsuccessful without organoids. In the past, researching misunderstood diseases often meant scanning affected individuals’ genomes for mutations in combination with the observation of animal brain development.  With organoids, however, the brain-like clumps form beautiful 3D displays of the brain’s natural conditions, far exceeding the accuracy of two-dimensional models. Now, the dimension of organoids are being taken advantage of to study other complex diseases such as Alzheimer’s and schizophrenia.

This new study upholds the belief that organoids can be used to analyze the nature of many diseases and disorders, like autism. Soon enough, thanks to organoids, scientists could be discovering how to manipulate and reverse certain key genes that cause autism.

By Maude Plucker

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