Seq-Scope Repurposes Sequencing Platform for Spatial Transcriptomics

University of Michigan Medical School researchers have developed a spatial transcriptomics technique that facilitates the visualization of all gene expression from a tissue sample. Until recently, researchers investigating the genes underlying disease have been limited because traditional imaging techniques only allow for the study of a handful of genes at a time.

The new technique uses high-throughput sequencing, instead of a microscope, to obtain ultra-high-resolution images of gene expression from a tissue slide. Seq-Scope, a spatial barcoding technology, enables a researcher to see every gene expressed, as well as single cells and structures within those cells, at high resolution.

"Whenever a pathologist gets a tissue sample, they stain it and look at it under the microscope, it's how they diagnose disease," explained Jun Hee Lee, senior author on a paper published today in Cell. "Instead of doing that, with our new method, we have made a microdevice that you can overlay with a tissue sample and sequence everything within it with a barcode with spatial coordinates."

Each so-called barcode is made up of a nucleotide sequence. Using these barcodes, a computer is able to locate every gene within a tissue sample, creating a Google-like database of all of the mRNAs transcribed from the genome.

"People have been trying to do this with other methods, such as microprinting, microbeads or microfluidic devices, but because of technological limitations, their resolution has been a distance of 20-100 micrometers. At that resolution you can't really see the level of detail needed to diagnose diseases," Lee said.

The team demonstrated the effectiveness of the technique using normal and diseased liver cells, successfully identifying dying liver cells, their surrounding inflamed immune cells and liver cells with altered gene expression. "This technology actually showed many known pathological features that people have previously discovered but also many genes that are regulated in a novel way that was unrecognized previously," said Lee. "Seq-Scope technology, combined with other single cell RNA sequencing techniques, could accelerate scientific discoveries and might lead to a new paradigm in molecular diagnosis."