There is a new technique described in Cell and developed by a group of researchers at the Broad Institute of MIT and Harvard for mapping cells. Scientists refer to this approach as DNA microscopy, revealing how biomolecules such as DNA and RNA are organized in cells and tissues to show spatial and molecular information that is not easily accessible through other microscopy methods. Also, DNA microscopy does not require specialized equipment, and it enables large numbers of samples to be processed simultaneously.
A post-doctoral associate at the Broad Institute and the first author of the study, Joshua Weinstein, said that DNA microscopy is an entirely new way of visualizing cells that captures both spatial and genetic information simultaneously from a single specimen. The method allows the researchers to see how genetically different cells, those comprising the immune system, cancer, or the gut, for instance, interact with one another and give rise to complicated multicellular life.
Researchers have developed tools in recent decades to collect molecular information from tissue samples, data that cannot be captured by either light or electron microscopes. Nevertheless, attempts to couple this molecular information with spatial data, to see how it is naturally arranged in a sample, are most times machinery-intensive with limited scalability.
But with DNA microscopy, the method takes a new approach to combining molecular information with spatial data with the use of DNA itself as a tool.
In the first place, the team adds small synthetic DNA tags to visualize a tissue sample which latches on to molecules of genetic material inside cells. Then, they replicated the tags by diffusing in "clouds" across cells and chemically reacting with each other, further combining and creating more unique DNA labels. They collect, sequence, and computationally decode the labeled biomolecules to reconstruct their relative positions and a visible image of the sample.
The researchers can calculate the locations of the different molecules with the interactions between these DNA tags, somewhat analogous to cell-phone towers triangulating the positions of different cell phones in their vicinity. It is scalable and efficient since the process only requires standard lab tools.
In this research, the reviewers demonstrate the ability to molecularly map the locations of individual human cancer cells in a sample by tagging RNA molecules. According to the researchers, DNA microscopy could be used to map any group of molecules that will interact with the synthetic DNA tags, including cellular genomes, RNA, or proteins with DNA-labeled antibodies.
Weinstein noted that DNA microscopy gives the scientists microscopic information without a microscopy-defined coordinate system. The team has used DNA in a way that is mathematically similar to photons in light microscopy. This technique allows them to visualize biology as cells see it and not as the human eye does. They are excited to use this tool in expanding their understanding of genetic and molecular complexity.
