Researchers have made great strides to understand early signs of autism.
Studies have found that certain factors like genetics, sleep deprivation, excess fluid in the brain-and brain size-can increase the risk of neurodevelopmental conditions, like autism.
Brain overgrowth has emerged as a new potential early biomarker of autism in recent years. Researchers are now seeking to understand why and how this is the case. New research in the lab of Jason Stein, PhD, a genetics expert at the UNC School of Medicine, has just identified two specific types of brain cells linked to increased brain growth.
The study-led by Rose Glass, PhD, and Nana Matoba, PhD-was conducted using meticulously grown stem cells that mimic the earliest stages of human brain development in a dish. The findings, which were published in Cell Stem Cell, show that this method can serve as a trusty and accurate modeling system for brain development, with which other scientists can use to study the early signs and causes of autism.
Madison "Rose" Glass, PhD. Credit: Sahin Lab
"Our research indicates that our participant-derived brain cell models, or brain organoids, are a good model system for studying early brain development," said Glass, who is now a postdoctoral research fellow at Boston Children's Hospital/Harvard Medical School. "We can now use this information to study cellular changes, like those caused by environmental toxin exposure, and how they contribute to autism."
Previous findings into brain size and autism were made by the Infant Brain Imaging Study (IBIS), a nationwide network of researchers studying autism through brain imaging scans of infants.
For the past 20 years, five universities, with the University of North Carolina-Chapel Hill as the lead site, have been studying the brains of infants with high familial risk for autism.
Glass, Matoba, and Stein collaborated with clinical colleagues and psychiatrists at the UNC School of Medicine and IBIS-including Jessica Girault, PhD, Mark Shen, PhD, and Joseph Piven, PhD-to create a first-of-its-kind cellular model of brain development in order to better understand what leads to bigger or smaller brains.
A graphical abstract showing reprogramming of cells for the project. Credit: Glass et al (2025).
Researchers first collected whole blood samples from eighteen individuals in the IBIS study. They then pulled out white blood cells, known as peripheral blood mononuclear cells, and "reprogrammed" them into pluripotent cells.
These unique cells can transform into any cell type, so researchers urged them to become a piece of tissue that mimics some of the structure and function of a human brain, known as a brain organoid.
A closer look revealed that changes in two brain cell types-neural progenitor cells and choroid plexus epithelial cells-are strongly associated with brain size of the participant from which they were derived.
Neural progenitors are cells that make other brain cells, including neurons. Choroid plexus epithelial cells make up a specialized layer of cells in the brain that help support the growth and repair of neural progenitor cells.
Researchers found that there was a clear relationship between gene expression levels in neural progenitor cells and larger brain size. The finding alone confirms that the model they created accurately mimics a human brain and brain development. With the accuracy of the brain organoid model confirmed, the Stein lab began planning even more brain development studies.
For example, the lab is currently investigating the potential effects of short- and long-term exposure to environmental toxicants, such as valproic acid (VPA), during pregnancy. The research project involves comparing brain organoids derived from individuals with and without autism to understand how exposure to these chemicals may lead to brain changes resulting in autism.
"We're now focusing on studying prenatal exposures that are associated with autism diagnosis," stated Stein. "We want to study how environmental toxicants impact early brain development, and how genetic risk factors can accentuate those effects."
