Scientists can now take snapshots of where and how thousands of genes are expressed in intact tissue samples, ranging from a slice of a human brain to the embryo of a fly.
The technique, reported recently in Science1, can turn a microscope slide into a tool for creating data-rich, three-dimensional maps of how cells interact with one another — a key to understanding the origins of diseases such as cancer. The methodology also has broader applications, enabling researchers to create, for instance, unique molecular ‘barcodes’ to trace connections between cells in the brain, a stated goal of the US National Institutes of Health's Human Connectome Project.
Previously, molecular biologists had a limited spatial view of gene expression, the process by which a stretch of double-stranded DNA is turned into single-stranded RNAs, which can in turn be translated into protein products. Researchers could either grind up a hunk of tissue and catalogue all the RNAs they found there, or use fluorescent markers to track the expression of up to 30 RNAs inside each cell of a tissue sample. The latest technique maps up to thousands of RNAs.
In a proof-of-principle study, molecular biologist George Church of Harvard Medical School in Boston, Massachusetts, and his colleagues scratched a layer of cultured connective-tissue cells and sequenced the RNA of cells that migrated to the wound during the healing process. Out of 6,880 genes sequenced, the researchers identified 12 that showed changes in gene expression, including eight that were known to be involved in cell migration but had not been studied in wound healing, the researchers say.
“This verifies that the technique could be used to do rapidly what has taken scientists years of looking at gene products one by one,” says Robert Singer, a molecular cell biologist at Albert Einstein College of Medicine in New York, who was not involved in the study.