Researchers have used so-called “mini-brains” to gain new insights into the cellular mechanisms behind brain growth in young children. This is a characteristic that is associated with autism. A study from the laboratory of Jason Stein, a genetics expert at the UNC School of Medicine, has shown that two specific types of brain cells play a key role in increased brain growth in early development.
The study, led by Rose Glass and Nana Matoba, uses advanced stem cell technology to mimic the earliest stages of human brain development in the laboratory. The results have been published in the leading scientific journal Cell Stem Cell and highlight the potential of this approach for research into neurodevelopmental disorders such as autism.
Brain growth as an early biomarker
It has long been known that autism is associated with various risk factors, including genetic predisposition, environmental influences and abnormalities in early brain development. In recent years, accelerated brain growth in infants has emerged as a possible early biomarker. However, the question of why this brain growth occurs remained largely unanswered.
Using brain organoids, three-dimensional cell structures that mimic certain characteristics of the human brain, the researchers were now able to investigate this question at the cellular level. ‘Our models, derived from the participants themselves, appear to be very suitable for studying early brain development,’ said Glass, now a postdoctoral fellow at Boston Children's Hospital/Harvard Medical School. ‘This opens the door to systematically analysing environmental factors, such as exposure to toxins.’
The study builds on data from the Infant Brain Imaging Study (IBIS), a large-scale American collaboration that has been tracking the brain development of babies with an increased familial risk of autism for twenty years. Blood samples were collected from eighteen participants in this cohort.
White blood cells were isolated from these samples and “reprogrammed” into pluripotent stem cells. These cells can develop into virtually any type of body cell. By directing them in a specific way, they grew into brain organoids that reflect aspects of the structure and function of the human brain.
Two cell types
Analysis of the organoids showed that changes in two types of brain cells are strongly correlated with brain size: neural progenitor cells and epithelial cells of the choroid plexus. Neural progenitor cells are precursor cells that produce new brain cells, including neurons. The choroid plexus plays a supporting role and is involved in, among other things, the production of cerebrospinal fluid and supporting growth and repair processes.
The clear relationship between gene expression in neural progenitor cells and larger brain size was striking. This confirms that the researchers' organoid model realistically mimics human brain development. This is a crucial step for follow-up research.
Digital and personalised insights
With the validation of this model, the research team is now focusing on new applications. For example, they are looking at the influence of prenatal exposure to environmental factors, such as the drug valproic acid (VPA), which has previously been linked to an increased risk of autism. By comparing organoids from people with and without autism, the researchers hope to better understand how genetic and environmental factors reinforce each other.
‘Our focus is now on prenatal exposures associated with an autism diagnosis,’ says Stein. ‘We want to understand how toxic substances affect early brain development and how genetic risks can amplify those effects.’
The study illustrates how advanced cell models and data analysis contribute to precision medicine in neurocare. By unravelling biological processes early and at an individual level, it opens up the prospect of earlier detection, more targeted prevention and, ultimately, more personalised care for children at increased risk of autism.
Eye tracking
Last year, we wrote (in Dutch) about Professor Ralph Adolphs, who sees eye tracking as one of the most effective methods for researching and better understanding autism. This technique records where subjects look when viewing images or videos. Research shows that people with autism tend to focus more on non-social elements, such as objects or patterns, while neurotypical individuals mainly look at faces. This offers valuable insights into differences in social cognition and emotion processing.
In his Emotion and Social Cognition Lab, Adolphs has been studying the neurobiological basis of social behaviour, including in autism, for decades. Eye tracking provides insight into underlying cognitive processes, but its use is still limited due to its high cost. Smartphone technology may make it more accessible in the future.
