TRISCO Reveals 3D RNA Structures at Cellular Resolution

A novel microscopy technique created by researchers at the Karolinska Institutet and Karolinska University Hospital allows for in-depth, three-dimensional (3D) RNA analysis at the cellular level in complete, undamaged mouse brains.

According to a recent study published in the journal Science, the new technique, known as TRISCO, has the potential to revolutionize the knowledge of how the brain functions in both healthy and diseased situations.

It has long been difficult to relate RNA data to its spatial context, particularly in entire 3D tissue volumes, despite significant advancements in RNA analysis. Three-dimensional RNA imaging of entire mouse brains is now feasible because of the TRISCO technique, which eliminates the need to cut the brain into thin slices as was previously required.

This method is a powerful tool that can drive brain research forward. With TRISCO, we can study the complex anatomical structure of the brain in a way that was previously not possible.”

Per Uhlén, Professor and Study Last Author, Department of Medical Biochemistry and Biophysics, Karolinska Institutet

The study examined up to three distinct RNA molecules concurrently. The researchers' next objective is to use a method known as multiplex RNA analysis to increase the number of RNA molecules that can be examined to about 100. This could yield even more specific details regarding illness states and brain function.

The TRISCO method creates new opportunities to gain a deeper understanding of the brain's complexity, which may result in the creation of novel therapies for a range of brain disorders.

We look forward to continuing our research and exploring the many possibilities offered by this new technique.”

Shigeaki Kanatani, Research Specialist and Study First Author, Karolinska Institutet

The study shows that TRISCO is appropriate for researching intact mouse brains and can also be utilized to investigate different tissues, including the kidney, heart, and lung, as well as larger brains like guinea pigs. Karolinska Institutet and Karolinska University Hospital collaborated on the project.

Our laboratory has several collaborations with clinically active researchers at Karolinska University Hospital. It is crucial for biomedical research that basic researchers and clinicians collaborate and understand each other.”

Per Uhlén, Professor and Study Last Author, Department of Medical Biochemistry and Biophysics, Karolinska Institutet

Source:
Journal reference:

Kanatani, S., et al. (2024) Whole-brain spatial transcriptional analysis at cellular resolution. Science. doi.org/10.1126/science.adn9947.

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