A breakthrough pathway to understand autism through brain organoids and gene screening
Researchers from a prominent independent biomedical institute have introduced a novel diagnostic framework for autism that relies on artificially engineered human brain tissues and the study of genetic mutations using these models. The findings were published in a leading scientific journal.
The CHOOSE system, which stands for CRISPR human organoids single-cell RNA sequencing, uses human brain organoids—three-dimensional tissue crafted from stem cells that replicate key aspects of brain architecture and function. This approach enables scientists to pinpoint vulnerable cell types and map the gene regulatory networks that influence autism spectrum disorders.
It is increasingly clear that many genes linked to a higher risk of autism play essential roles in cerebral cortex development. While clinical studies have demonstrated that multiple genetic alterations can contribute to autism, the precise ways in which these mutations disrupt brain development remain only partially understood. Traditional animal models face limitations because human brain development contains unique features that are not fully captured in other species.
To bridge this gap, researchers have developed a high-throughput method to screen all key transcription regulatory genes implicated in autism. A regulatory gene encodes a protein that can activate or repress the transcription of other genes, shaping how networks evolve during development. This capability enables the creation of brain models by introducing different genes of interest, thereby increasing the efficiency and scope of genetic screening.
In the CHOOSE system, each organoid cell can carry at most one mutation in a gene associated with autism. Scientists monitor the impact of each specific mutation at the level of single cells and track its developmental trajectory. The outcome of each mutation can be observed in a single experiment, markedly reducing the time required for analysis.
Researchers observed that mutations in a set of thirty-six autism-associated genes share some common molecular mechanisms, revealing shared pathways that underlie diverse genetic routes to autism. Yet some cell types prove more susceptible to mutations linked to autism, with neuronal precursors identified as particularly vulnerable during critical periods of brain development.
A separate line of inquiry notes that associations between common intestinal infections and neurodegenerative processes such as Alzheimer’s disease have been explored, highlighting the ongoing interest in how systemic factors might influence neural health.