The approximately 30,000 genes that make up the human genome contain the instructions essential to life. Yet each of our cells expresses only a subset of these genes in their daily functioning. The difference between a heart cell and a liver cell, for example, is determined by the genes expressed – and the correct expression of genes can make the difference between health and disease.
Until recently, researchers studying the genes underlying the disease were limited because traditional imaging techniques can only study a handful of genes at a time.
A new technique developed by Jun Hee Lee, Ph.D., and his team at the University of Michigan Medical School, part of Michigan Medicine, uses high-throughput sequencing, instead of a microscope, to obtain Ultra-high resolution gene expression images from a tissue slide. The technology, which they call Seq-Scope, allows a researcher to see every gene expressed, along with individual cells and structures within those cells, at an incredibly high resolution: 0.6 microns or 66 times smaller. than a human hair – beating current methods by orders of magnitude.
“Every time a pathologist gets a tissue sample, they stain it and examine it under a microscope – that’s how they diagnose a disease,” said Lee, associate professor in the Department of Molecular and Integrative Physiology. “Instead of doing that, with our new method, we created a micro-device that you can overlay with a tissue sample and sequence everything in it with a barcode with spatial coordinates.”
Each so-called barcode is made up of a sequence of nucleotides – the motif of A, T, G, a C – found in DNA. Using these barcodes, a computer is able to locate each gene in a tissue sample, creating a Google-like database of all the mRNAs transcribed from the genome.
“People have tried to do this with other methods, such as micro-printing, microbeads, or microfluidic devices, but due to technological limitations their resolution has been from a distance of 20 to 100 micrometers. this resolution, you can’t really see the level of detail needed to diagnose disease, ”Lee said.
Lee adds that the technology has the potential to create a systematic, unbiased way of analyzing genes.
“Every time we do science we had to make a hypothesis about the role of two or three genes, but now we have data at the genome scale at the microscopic scale and a lot more knowledge about what is going on. passes through the tissue of that patient or model animal. “
This knowledge could be used to understand why some patients respond to certain drugs while others don’t, Lee said.
The team demonstrated the effectiveness of the technique using normal and diseased liver cells, successfully identifying dying liver cells, surrounding inflamed immune cells, and liver cells with altered gene expression.
“This technology has actually shown many known pathological features that people have already discovered, but also many genes that are being regulated in new ways that were not previously recognized,” Lee said. “Seq-Scope technology, combined with other single-cell RNA sequencing techniques, could accelerate scientific discoveries and could lead to a new paradigm in molecular diagnostics.”
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Material provided by Michigan Medicine – University of Michigan. Original written by Kelly Malcom. Note: Content can be changed for style and length.