Researchers at Karolinska Institutet and Karolinska University Hospital have developed a powerful microscopy method called TRISCO that enables detailed three-dimensional (3D) RNA analysis at cellular resolution in whole, intact mouse brains. It is also applicable to other tissues like the kidney, heart, and lung, making it a valuable tool in biomedical research.
For decades, the challenge of linking RNA data to its precise spatial context in 3D tissue has been a major obstacle. Traditional methods required slicing tissues into thin sections, often losing critical spatial information. TRISCO changes the game by allowing 3D RNA imaging of entire mouse brains without sectioning, preserving the brain's intricate structure.
"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," said Professor Per Uhlén, senior author of the study published in Science and professor at Karolinska Institutet's Department of Medical Biochemistry and Biophysics.
Image of a mouse brain. (Image Credit: Kanatani, S. et al. / Science)
Breaking new ground in RNA imaging
Using TRISCO, the researchers successfully analyzed up to three different RNA molecules simultaneously within the brain's complex architecture. They aim to enhance the method further by incorporating multiplex RNA analysis, allowing the study of around a hundred RNA molecules at once. This could provide unprecedented insights into how RNA variations influence brain function in health and disease.
"We look forward to continuing our research and exploring the many possibilities offered by this new technique," said Shigeaki Kanatani, the study's first author and a research specialist in Uhlén's laboratory.
Versatility beyond the brain
TRISCO's applications extend beyond mouse brains. The researchers demonstrated its effectiveness in studying larger brains, such as those of guinea pigs, and various tissues, including kidney, heart, and lung. This versatility makes TRISCO a valuable tool across multiple fields of biomedical research.
The study highlights the importance of collaboration between basic researchers and clinicians. "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," Uhlén added.
Original Publication:
Kanatani, S. et al.: Whole-brain spatial transcriptional analysis at cellular resolution. Science (2024); DOI: 10.1126/science.adn9947
