Data Science Seminar
September 29, 2020
Martin Aryee, PhD
Assistant Professor of Pathology, Harvard Medical School
Assistant Molecular Pathologist, Massachusetts General Hospital
Zoom link: https://dfci.zoom.us/j/95524743149?pwd=SzN4cjJZUnhsNVl3dXNmZjZ1N3F4QT09
Abstract: The spatial organization of biological systems can impart additional functionality beyond that of the individual components. This is true at a range of scales – from cells in a tissue to individual genes and regulatory elements in a single genome. High-throughput assays that permit spatial measurements have advanced greatly in the past decade and revealed oncogenic architectural alterations in tumors at the tissue, cellular and chromosome levels. Here I will discuss tumor spatial organization in gastrointestinal malignancies at two different scales. First, I will describe how we used single-cell RNA-Seq and RNA in situ hybridization in pancreatic cancer to identify cell state and tissue architecture changes induced by contact with stromal cancer-associated fibroblasts (CAFs). We analyzed the spatial architecture of cell states in 195 pancreatic tumors, mapping over 300,000 individual cancer cells. We were able to classify different types of tumor glands based on their cell-type composition, and show that these functional units can be used to characterize tumors in ways not evident from analyses of dissociated single cells. Second, I will discuss findings from a recent study of 3D genome organization within colon cancer cell nuclei. We found oncogenic changes at the level of regulatory chromatin loops and topologically associated domains (TADs), but the most surprising and striking change involves a large-scale repackaging of heterochromatin that appears to restrain tumor progression, representing a failed anti-tumor epigenetic brake.