Thanks to advances in microscopy, Mayo Clinic experts are examining gene expression in three dimensions to better understand and treat disease.
Understanding the molecular underpinnings of disease is one of the keys to developing new treatments and cures. Transcriptomics — the study of gene expression — is one tool that can be leveraged to understand how cells and tissues respond in health and disease.
Now, thanks to an innovative technology known as spatial transcriptomics, Mayo Clinic experts are able to examine how genes are expressed in a tissue sample in three dimensions, providing unprecedented insights into cellular relationships and tissue structure.
“Omics” is a term used to describe the collective study of biological molecules, from genes to proteins and beyond. Transcriptomics specifically refers to the study of gene expression — how our genetic code, or DNA, gets transcribed into RNA, which is then used to build proteins.
Understanding gene expression can help scientists better understand human biology by providing insights into where and when genes are turned on and off during development and disease. This is important for knowing how different cells function and how they interact with one another in the healthy body, as well as what changes when someone gets sick. Transcriptomics can be especially helpful for identifying biomarkers of disease, which can aid in diagnosis and treatment.
Traditionally, transcriptomics is focused on understanding the overall gene expression within a tissue — for example, a researcher might examine the gene expression of healthy pancreatic tissue and compare it to the gene expression in a pancreatic cancer tumor, or even how a single cancer cell compares to a single healthy one. But these approaches do not preserve organizational information about how genes are expressed in different areas of a tissue or a tumor, or whether there might be variations in that expression across a sample.
Spatial transcriptomics is radically advancing our understanding of biology thanks to the fact that with this technology researchers can see not just what genes are being expressed, but exactly where a gene is active within a tissue. This means that scientists can examine the gene expression within individual cells while preserving the broader context of how those cells are interacting with their neighbors.
This feat is accomplished through tissue preservation and microscopy techniques that maintain the tissue’s structure while measuring the expression of many different genes across the sample. This produces a detailed map of how different cells are behaving and communicating within, for example, a biopsy from a cancerous tumor.
In cancer, this is particularly impactful because it means that researchers and pathologists can now see exactly where certain genes are active within a tumor, allowing for a clearer picture of the molecular dynamics of the disease and opening new avenues for treatment.
Mayo Clinic’s investment in spatial biology is another step toward truly personalized medicine. Led by Tamas Ordog, M.D., and Jeong-Heon Lee, Ph.D., a team of Mayo Clinic scientists are building a first-of-its-kind research core dedicated entirely to spatial biology, beginning with spatial transcriptomics. Supported by machine learning and artificial intelligence tools that analyze the 3D data generated from patient samples, they say this tool will reimagine how diseases are classified and treated.
This technology is already transforming how Mayo Clinic approaches complex cancers, as researchers work to create new ways to examine biopsy samples to predict which therapies will be most effective based on a tumor's unique cellular architecture and molecular signatures.
As the spatial biology technique develops, the team plans to build detailed tissue atlases to map the progression of various diseases in unprecedented detail, potentially revealing early intervention points and novel therapeutic targets that would otherwise remain hidden in the complex biology of human disease.
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