Researchers develop new method for capturing dynamic processes in individual cells

Researchers at Karolinska Institutet and Harvard Medical School report in the journal Nature that they have developed a technique for capturing dynamic processes in individual cells. Apart from studying disease processes, the method can be used to observe in detail how specialized cells are formed during embryonic development.

The body is composed of specialized cells that give each organ its unique function. The brain, for instance, is made up of hundreds of different kinds of neurons, while the kidneys have specialized cells for filtering blood and the heart muscle cells have a built-in pacemaker function. Organs are formed as the embryo develops through a process of gradual specialization. The fertilized egg divides and as more cells are formed they start to take on more specific functions. Similar processes are also found in tumors, which gradually develop into a kind of organ with blood vessels and supporting cells that help the tumor grow.

Difficult to study dynamic processes

What determines the unique function of each cell is the specific genes that are active within it. In neurons, for example, genes are activated that control electrical signals, while muscle cells use genes for motor proteins. In recent years, Swedish and international researchers have developed methods for mapping the cellular composition of complex tissues by studying the gene activity of individual cells. The downside of these methods is that they are destructive. Measuring gene activity of individual cells involves destroying the cells so that their content can be analyzed, which makes it difficult to study dynamic processes.

"It's like a photograph in which all movement is frozen in time," explains Professor Sten Linnarsson at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, and one of the researchers who led the study. "We've now developed a new method that measures not only genetic activity but also changes in this activity in individual cells. You can compare this to a photo captured with a long exposure, which results in motion blur: stationary objects are sharp while objects in motion are blurred. Objects moving quickly are blurrier, and the direction of movement is revealed by the direction of blur."

Method to be used to study tumor formation, wound healing and the immune system

The new method exploits the fact that when genes are activated, a series of RNA molecules are formed in a certain order. By separating out these molecules, the researchers can work out if a gene has just been activated or if, for example, it is about to be switched off.

"This new method allows us to observe in detail how specialized cell types are formed in the embryo, including the human embryo," says Professor Linnarsson. "It can also be used to study dynamic disease processes, such as tumor formation, wound healing and the immune system."