December 25, 2023

A breakthrough in autism research has been achieved with the CHOOSE system developed by researchers at IMBA and ETH Zurich. This technology enables detailed study of genetic mutations in human brain organoids, providing deep insight into the mechanisms underlying autism and paving the way for applications in broader disease research.

The CHOOSE system is an innovative approach that combines brain organoids and genetics to transform autism research by enabling detailed analysis of mutations and their impact on brain development.

Does the human brain have an Achilles heel that ultimately leads to autism? With an innovative new system that combines brain organoid technology and complex genetics, researchers are now able to identify multiple It is now possible to comprehensively test the effects of mutations in parallel at the single-cell level.

The technology was developed by researchers from the Knoblich Group at the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences and the Treutlein Group at ETH Zurich and aims to identify the vulnerable cell types that underlie autism spectrum disorders. Enables identification of gene regulatory networks. This innovative method provides unparalleled insight into one of the most complex disorders that challenges the human brain and brings much-needed hope to clinical research in autism.

Human brain development and ASD riskcompared to other animals seed, the human brain has a mind of its own. The human brain relies on uniquely human processes to develop and is able to build a complex, layered and interconnected cortex. These unique processes also predispose humans to neurodevelopmental disorders.

As an example, many genes confer a high risk of developing autism spectrum disorder (ASD) is essential for cortical development. Clinical studies have shown a causal link between multiple genetic mutations and autism, but researchers still do not understand how these mutations lead to impaired brain development. . Additionally, the uniqueness of human brain development limits the use of animal models.

Only human brain models can reproduce the complexity and specificity of the human brain,” says IMBA Scientific Director Jürgen Knoblich, one of the study’s corresponding authors.

Left half: Confocal image of CHOOSE (CRISPR-humanorganoids-scRNA-seq) human brain organoid mosaic system. Cells with mutations are shown in red. Right half: Mosaic depiction of different colors representing a single cell. Each cell carries a mutation in one high-confidence autism gene.

Credit: ©Knoblich Lab / IMBA-IMP Graphics

Innovative CHOOSE system for genetic screeningTo unravel this black box, researchers from IMBA and the research group of Jürgen Knoblich and Barbara Treutlein at ETH Zurich have identified a complete set of key transcriptional regulatory genes associated with autism. We have developed a screening technology. This development is particularly impactful because it allows for the simultaneous testing of genes of interest within a single mosaic organoid, marking the beginning of an era of complex, efficient, and rapid genetic screening in human tissues.

Source: scitechdaily.com