By Anne Trafton 

Using a novel technique for expanding tissue, MIT and Harvard Medical School researchers have devised a way to label individual molecules of messenger RNA within a tissue sample and then sequence the RNA.

This approach offers a unique snapshot of which genes are being expressed in different parts of a cell, and could allow scientists to learn much more about how gene expression is influenced by a cell’s location or its interactions with nearby cells. The technique could also be useful for mapping cells in the brain or other tissues and classifying them according to their function.

“Gene expression is one of the most fundamental processes in all of biology, and it plays roles in all biological processes, both healthy and disease-related. However, you need to know more than just whether a gene is on or off,” says Ed Boyden, the Y. Eva Tan Professor in Neurotechnology and a professor of biological engineering, media arts and sciences, and brain and cognitive sciences at MIT. “You want to know where the gene products are located. You care what cell types they’re in, which individual cells they play roles in, and even which parts of cells they work in.”

In a study appearing today in Science, the researchers showed that they could use this technique to locate and then sequence thousands of different messenger RNA molecules within the mouse brain and in human tumor samples.

The senior authors of the study are Boyden, an investigator at the MIT McGovern Institute and the Howard Hughes Medical Institute; George Church, a professor of genetics at Harvard Medical School; and Adam Marblestone, a former MIT research scientist. The paper’s lead authors are Shahar Alon, a former MIT postdoc who is now a senior lecturer at Bar-Ilan University; Daniel Goodwin, an MIT graduate student; Anubhav Sinha ’14 MNG ’15, an MIT graduate student; Asmamaw Wassie ’12, PhD ’19; and Fei Chen PhD ’17, who is an assistant professor of stem cell and regenerative biology at Harvard University and a member of the Broad Institute of MIT and Harvard.