A human model for autism

How does autism develop? Which genes and cells in the human brain contribute to it? A new brain organoid model allows researchers from the Department of Biosystems at ETH Zurich in Basel and colleagues from Vienna to investigate these questions in human cells. Organoids are microtissue spheroids that are grown from stem cells and have a similar structure to real organs – in other words, they are miniature organs of sorts.

With them, and with a new method for modifying genes within these organoids using the CRISPR-​Cas gene scissors, the researchers found out which genetic networks in which cell types in the brain are responsible for the development of autism. “Our model offers unparalleled insight into one of the most complex disorders affecting the human brain and brings some much needed hope to clinical autism research,” says Jürgen Knoblich, Professor and Scientific Director of the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences in Vienna and co-​author of the study.

Changing different cells in different ways

This new method enabled the researchers to genetically modify the cells of a brain organoid in a mosaic-​like fashion and then study them systematically. Specifically, the scientists altered one of 36 different genes associated with autism in each of the individual cells and studied the resulting effects. “We can see the consequences of every mutation in a single experiment, thus reducing the analysis time drastically when compared to conventional methods,” Knoblich says.

The new method was developed by researchers at the IMBA in Vienna, based on previous methods. In the current study, the group led by Barbara Treutlein, Professor of Quantitative Developmental Biology at ETH Zurich, incorporated the computer-​assisted analysis of the raw research data: changing multiple genes in parallel in a human organoid and analysing the resulting effects at the level of thousands of individual cells creates a vast amount of data. To manage it all, Treutlein and her team used state-​of-the-art bioinformatics methods.

The advantage of human tissue

In human disease research, organoids offer advantages over research using lab animals: unlike in lab animals, human genes and cells can be studied in organoids. These advantages are particularly significant in neuroscience, as the specific processes responsible for the development of the human cerebral cortex are unique to the human brain. Neurodevelopmental disorders in humans are due in part to these human-​specific processes in brain development. For example, many human genes that confer an increased risk for an autism spectrum disorder are genes that are critical for cortex development.

Read on >> Find full-length ETH News.