Gene activity visualized for the first time in thousands of single cells

Gene activity visualized for the first time in thousands of single cells

The technique is based upon the combination of robots, an automated microscope and a supercomputer.

According to a news release from the University of Zurich, gene activity has been visualized for the first time in thousands of single cells.

Biologists have created a technique to visual the activity of genes in single cells. The technique is extremely efficient. So efficient, in fact, that a thousand genes can be examined in parallel in ten thousand single human cells. Practical uses for this technique can be found in the fields of basic research and medical diagnostics. The new technique reveals that the activity of genes, and the spatial arrangement of the resulting transcript molecules, completely differ between single cells.

Whenever cells activate a gene, they generate gene specific transcript molecules, which make the capacity of the gene accessible to the cell. The determination of gene activity is a typical job in medical diagnostics. Current technologies measure the activity of genes by determining the quantity of transcript molecules. However, these technologies can neither determine the quantity of transcript molecules of one thousand genes in ten thousand single cells, nor the spatial arrangement of transcript molecules within a single cell. The new technique enables a parallel measurement of the quantity and spatial arrangement of the single transcript molecules in ten thousand single cells.

The technique is based upon the combination of robots, an automated microscope and a supercomputer.

“When genes become active, specific transcript molecules are produced. We can stain them with the help of a robot,” says PhD student Thomas Stoeger.

Consequently, fluorescence microscope photos of brightly glowing transcript molecules are produced. Those images were studied with the supercomputer Brutus. With this technique, one thousand human genes can be examined in ten thousand single cells.

Professor Lucas Pelkmans of the University of Zurich says that the benefits of this technique are the high number of singles cells and the possibility to examine the spatial arrangement of the transcript molecules of many genes.

The examination of the new data reveals that individual cells differentiate themselves in the activity of their genes. While biologists had been assuming a high variability in the quantity of transcript molecules, they were amazed to find a strong variability in the spatial arrangement of transcript molecules within single cells and between multiple single cells. The transcript molecules took on unique patterns.

“We realized that genes with a similar function also have a similar variability in the transcript patterns,” says PhD student Nico Battich. “This similarity exceeds the variability in the amount of transcript molecules, and allows us to predict the function of individual genes.”

The biologists believe that transcript patterns are a neutralizer to the variability in the quantity of transcript molecules. Therefore, such patterns would be to blame for the strength of processes within a cell.

“Our method will be of importance to basic research and the understanding of cancer tumors because it allows us to map the activity of genes within single tumor cells,” adds Pelkmans.

The study’s findings are described in greater detail in the journal Nature Methods.

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