“Spatially resolved transcriptomics” was the “Method of the Year 2020” according to Nature Methods. But what is this technology, and what can we do with it? A recent study from the Lieber Institute for Brain Development provides an example.

First, a thin slice of biological tissue is placed on a specialized microscope slide. The tissue slice is photographed under the microscope. RNA molecules within the tissue are captured and sequenced to measure gene expression. The microscope photo helps determine which genes were expressed in specific parts of the tissue slice, revealing how gene expression varies across the tissue.

The approach is suitable for studying the human brain, especially the cerebral cortex which is organized into well-defined layers. Each layer has its own specific types of cells with a distinctive shape, molecular identity, and connectivity with the rest of the brain. Earlier studies measured the gene expression in layers of the cortex one gene at a time. In contrast, the recent study from the Lieber Institute measured layer-specific expression across all expressed genes, called the “transcriptome”.

Using brain tissue from three donors, the researchers measured gene expression across the layers of the prefrontal cortex – a brain region implicated in psychiatric and neurological diseases. They confirmed the previously described layer-specific expression pattern of several genes and identified additional genes which also show a layered pattern of expression. Further, the researchers found layer-specific expression of genes linked with schizophrenia and autism, a finding that could enhance our understanding of the mechanisms underlying these disorders.

The results of the study were made freely available to the community, representing a valuable resource for the many researchers who will undoubtedly apply this technology to further explore human cortical gene expression in the near future.