A chemical approach to imaging cells from within


Researchers develop a new microscopy system to create cell maps, using chemical reactions to encode spatial information.

A visualization of the data for a sample provided by DNA microscopy, with random colors attributed to individual inferred cells.

A visualization of the data for a sample provided by DNA microscopy, with random colors attributed to individual inferred cells.

Credit: Joshua Weinstein, Broad Institute

The following press release was released today by Broad Institute of MIT and Harvard.

A team of researchers at the McGovern Institute and the Broad Institute of MIT and Harvard have developed a new technique for mapping cells. The approach, called DNA microscopy, shows how biomolecules such as DNA and RNA are organized into cells and tissues, revealing spatial and molecular information that is not easily accessible through other microscopic methods. DNA microscopy also does not require specialized equipment, allowing a large number of samples to be processed simultaneously.

"DNA microscopy is a whole new way of visualizing cells that capture spatial and genetic information simultaneously from a single specimen," says first author Joshua Weinstein, a postdoctoral associate at the Broad Institute. "This will allow us to see how genetically unique cells – those that comprise the immune system, cancer, or gut, for example – interact with one another and give rise to complex multicellular life."

The new technique is described in Cell. Aviv Regev, a senior fellow at the institute and director of the Klarman Cell Observatory at the Broad Institute and professor of biology at MIT, and Feng Zhang, a member of the Broad Institute's central institute, a research fellow at the McGovern Institute for Brain Research at MIT James and Patricia Poitras Professor of Neuroscience at MIT, are co-authors. Regev and Zhang are also researchers at the Howard Hughes Medical Institute.

The Evolution of Biological Imaging

In the last decades, researchers have developed tools to collect molecular information from tissue samples, data that can not be captured by light or electron microscopes. However, attempts to couple this molecular information with spatial data – to see how it is naturally organized in a sample – are often machine intensive, with limited scalability.

DNA microscopy takes a new approach to combining molecular information with spatial data, using DNA itself as a tool.

To visualize a tissue sample, researchers first add small labels of synthetic DNA, which bind to molecules of genetic material inside the cells. The tags are then replicated, diffused into "clouds" through the cells and chemically reacting with each other, combining and creating more unique DNA labels. The labeled biomolecules are collected, sequenced and decoded computationally to reconstruct their relative positions and a physical image of the sample.

The interactions between these DNA tags allow researchers to calculate the location of different molecules – somehow analogous to cell phone towers that triangulate the locations of different cell phones nearby. Because the process only requires standard lab tools, it is efficient and scalable.

In this study, the authors demonstrate the ability to molecularly map the locations of human cancer cells in a sample, marking RNA molecules. DNA microscopy can be used to map any group of molecules that will interact with synthetic DNA tags, including cellular genomes, RNA or proteins with DNA-labeled antibodies, according to the team.

"DNA microscopy gives us microscopic information without a coordinate system defined by the microscope," says Weinstein. "We use DNA mathematically similar to photons in light microscopy. This allows us to visualize biology as the cells see it and not as the human eye. We are excited to use this tool to expand our understanding of genetic and molecular complexity. "

Funding for this study was provided by the Simons Foundation, Klarman Cell Observatory, NIH (R01HG009276, 1R01- HG009761, 1R01- MH110049 and 1DP1-HL141201), New York Stem Cell Foundation, Simons Foundation, Paul G. Allen Family Foundation, Vallee. Foundation, the Center for Research on Affective Disorders at MIT, Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT, J. and P. Poitras, and R. Metcalfe.

The authors have applied for a patent on this technology.

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