Scientists have developed some incredibly advanced ways to actually visualize gene activity in tissues. A sample of tissue can be processed to analyze the genetic material inside, and researchers can measure the amounts of various genes that are expressed in that tissue. There are always ways to probe for specific gene transcripts in a slice of tissue, to see where that gene is being expressed in the tissue. But as technologies advanced, scientists were able to develop a tool known as spatial transcriptomics, in which the active genes in a tissue could be both detected, visualized, and measured where they are in intact tissue.
There have also been improvements in that tool as well, such as Seq-Scope, which shows the location and level of gene activity not only in tissues, but also the gene activity that occurs inside of cells at the microscopic level. This tool captures every messenger RNA (mRNA) molecule, which represents the active genes in a tissue, at unprecedented detail. Now the team behind that improvement has taken it further, so that imaging resolution is even better. The work has been reported in Nature Communications.
This latest technique is called Seq-Scope-eXpanded, or Seq-Scope-X. It enables scientists to visualize the barriers between cells and the genetic transcripts they contain, even when they are in different parts of the cell, such as the cytoplasm or nucleus.
“We wondered what we might see if we had even better resolution, but we realized that that is actually physically impossible,” said Jun Hee Lee, Ph.D., Professor of Molecular & Integrative Physiology at U-M Medical School.
In Seq-Scope, the mRNA transcripts are identified with an Illumina sequencing machine, which uses certain molecules that limit the resolution. To overcome this challenge, the researchers expanded the tissues that were being analyzed. Expansion microscopy has been around for awhile, but it has been integrated with other tools, like Seq-Scope, to make it more powerful.
"We made the tissue bigger and then analyzed it using our SeqScope methodology," explained Lee. "And we were able to show that it indeed precisely and accurately captures the transcriptome from the tissue."
The method goes beyond Seq-Scope. "We have kind of pushed that limit by another order of magnitude so we can get richer information. This technology is really moving fast, with resolution improving roughly four-fold each year for nearly a decade,” said Lee.
Sources: University of Michigan, Nature Communications
