TUMORLY: a novel largescale spatial transcriptomics technology to decipher the role of chromosome Y loss in tumor biology

Objective

Results from my ERC funded DIALOY and HEARTLY projects establish that during-life acquired loss of chromosome Y (LOY) in blood cells contribute to all major causes of male deaths, incl. various types of cancer, Alzheimer’s disease and cardiovascular disease. Recent single cell analyses identify LOY-cells in the blood of all studied men and in many other tissues, suggesting that LOY might be an inevitable result of living. How LOY in blood contributes to increased risk for diseases manifesting in other organs is a fundamental question that needs further exploration. We recently provided the first evidence that LOY in blood is causally related to reduced lifespan, by a profibrotic TGFβ-driven disease mechanism. Furthermore, LOY in tumor cells is common and drive male tumorigenesis by evasion of adaptive immunity in the tumor microenvironment. However, little is known about the interactions of LOY in cancer cells and tumor infiltrating leukocytes, both associated with male tumorigenesis. In TUMORLY, the main objective is to develop a new spatial method that enables largescale and true single-cell transcriptomic analyses of tumor specimens. This is not possible by existing spatial technologies. The novel method will first be used for portraying the transcriptomic landscape in male colon cancer biopsies. This will allow for detailed exploration of disease mechanisms mediated by Y loss in tumor cells and infiltrating leukocytes simultaneously. Going forward, our method promises to become the next generation spatial technology, owing to properties such as its single-cell resolution and feasibility with other omics, such as genomics, epigenomics and proteomics. Combined with its affordability and ease-of-use, the method has the potential to revolutionize and democratize single-cell spatial biology. I envision that a successful implementation of the new method in research settings will facilitate important discoveries that will benefit patients and societies at large