A group of cells captured with a traditional optical microscope (left) and with DNA microscopy (right)

Weinstein et al./Cell

Researchers use DNA to take pictures of cells

To look at a cell, you used to need a microscope. Now, researchers have found a way to view cells by using their own genetic material to take snapshots. The technique—called DNA microscopy—produces images that are less clear than those from traditional microscopy, but that could enable scientists to improve cancer treatment and probe how our nervous system forms.

“DNA microscopy is an ingenious approach,” says geneticist Howard Chang of the Stanford University School of Medicine in Palo Alto, California, who wasn’t connected to the research. “I think it will be used.”

To make the DNA microscope, postdoc Joshua Weinstein of the Broad Institute of in Cambridge, Massachusetts, and colleagues started with a group of cells in a culture dish. By creating DNA versions of the RNA molecules in the cells, they produced a large number of DNA molecules they could track. They then added tags—short pieces of DNA—that latched onto these DNA duplicates. Next, the scientists mixed in chemicals that produce multiple copies of these tags and the DNA molecules they connect to. As these copies built up, they started to drift away from their original location. When two wandering DNA molecules ran into each other, they linked up and spawned a unique DNA label that marked the encounter.

These labels are crucial for capturing a DNA image of the cells. If two DNA molecules start out close to each other, their diffusing copies will hook up frequently and produce more labels than two DNA molecules that start out farther apart. To count the labels, the researchers grind up the cells and analyze the DNA they contain. A computer algorithm can then infer the original positions of the DNA molecules to generate an image.

In a sense, Weinstein says, the original DNA molecules are like radio towers that send messages in the form of DNA molecules to each other. Researchers can detect when one tower communicates with another one nearby and use the pattern of transmissions among towers to map their locations.

To determine how well the technique works, the researchers tested it on cells carrying genes for either green or red proteins. The image created with DNA microscopy was not as sharp as one the researchers obtained with a light microscope, but it distinguished the genetically distinct red and green cells, the team reports today in Cell. In addition, Weinstein says, it captured the arrangement of the cells. That ability could be useful in analyzing a sample from, say, an organ in a human body. The technique can’t yet reveal fine details within cells, however.

“The goal is not to replace optical microscopy,” Weinstein says. But DNA microscopy can do some things optical microscopy can’t. For instance, optical microscopy often can’t distinguish among cells with DNA differences, such as tumor cells with specific mutations or immune cells, which are often genetically unique after shuffling their DNA. Weinstein says DNA microscopy may help improve certain cancer treatments by identifying immune cells that can attack tumors. As our nervous system develops, cells often produce unique RNAs that enable them to make specialized proteins, and the technique could also help researchers investigate these cells.

The technique is “pretty cool,” says molecular technologist Joakim Lundeberg of the KTH Royal Institute of Technology in Stockholm, who helped develop an approach for visualizing RNA in cells. But he cautions that the study is preliminary and that researchers still need to determine the technique’s capabilities. DNA microscopy would be valuable if it could produce 3D images of cells in a sample, he says. “They need to demonstrate this in a tissue to really understand how useful it is.”