A groundbreaking technology, Seq-Scope, developed at the University of Michigan, has opened up new frontiers in gene activity mapping. This innovation allows researchers to visualize gene expression within intact tissue at a microscopic level, offering an unprecedented level of detail. The team, led by Dr. Jun Hee Lee, has recently taken this technology to the next level, as described in their recent publication in Nature Communications.
"We wanted to push the boundaries and see what we could uncover with enhanced resolution," shared Dr. Lee, a Professor at the U-M Medical School. However, they soon realized that there was a physical barrier to their ambitions.
The challenge lies in the preparation of tissue slides for sequencing. The process involves diffusing molecules from the tissue to the array, but this diffusion is limited to approximately one micron. To overcome this hurdle, Dr. Lee's team employed a clever strategy: they made the tissues larger by embedding them in hydrogel and infusing them with water, effectively expanding the tissue.
This innovative approach was conceived by Angelo Anacleto, a graduate student on the team, who collaborated with Dr. Hee-Sun Han, a Professor of Chemistry at the University of Illinois Urbana-Champaign, to incorporate chemical tissue expansion methods into Seq-Scope.
"By making the tissue bigger, we were able to analyze it with our SeqScope methodology and demonstrate its precision and accuracy in capturing the transcriptome from the tissue," explained Dr. Lee.
The team's newly developed method, Seq-Scope-eXpanded (Seq-Scope-X), offers an even greater resolution, allowing them to distinguish between cells and even the transcripts of different cellular structures, such as the nucleus and cytoplasm. This level of detail was made possible by the computational methods developed by Dr. Hyun Min Kang, a Professor of Biostatistics at the U-M School of Public Health.
Dr. Lee believes that this tool has the potential to unlock new discoveries that were previously inaccessible. "We have pushed the limits of resolution, enabling us to gather richer information. The technology is advancing rapidly, with resolution improving by approximately four times each year for nearly a decade. We are proud to be at the forefront of this exciting development at the University of Michigan."
The paper, titled "Seq-Scope-eXpanded: spatial omics beyond optical resolution," is available in Nature Communications (DOI: 10.1038/s41467-026-69346-8).
What do you think about this groundbreaking research? Could this technology revolutionize our understanding of gene activity? Share your thoughts in the comments below!
