In this project we study non-coding RNA (ncRNA)—pieces of RNA that don’t make proteins but help control how cells work. We analyzed ncRNA expression in more than 50 human organs. The testis had the most RNAs that are unique to a single organ, with certain brain regions next. Every organ had some highly specific ncRNAs, suggesting these are important for organ function. We based the first analysis on data from a large public resource called GTEx (Genotype-Tissue Expression). To verify these findings, we are now repeating this work using an independent resource, the Human Protein Atlas. We also performed a different type of analysis to look at which cell types within these organs express these ncRNAs. Highly specialized cells - like sperm cells in the testis or hepatocytes in the liver - showed the most cell-type-specific ncRNAs. Many of these overlapped with the organ-specific ones, since those cell types are found in only one organ. Next, we focused on endothelial cells, the thin layer of cells that lines all blood vessels. These cells regulate blood flow and help the body respond to infection or injury. We identified a set of ncRNAs that are specific to endothelial cells across the body and confirmed they are present in endothelial cells grown in the lab. We also tested how their levels change under conditions relevant to blood vessels, such as simulated blood flow or exposure to inflammatory signals. Several ncRNAs responded strongly, indicating that they could have key roles in the endothelial cell response. We are now studying their function using laboratory-made models of blood vessels.
Messenger ribonucleic acid (mRNA) is a molecule that helps to make proteins, which are the building blocks of all cells. Non-coding RNA (ncRNA) is a type of RNA that doesn't make proteins but has other roles in the cell. Recent research has shown that a type of ncRNA called long ncRNA (lncRNA) can be involved in many diverse cellular processes, including in growth and differentiation, as well as in disease development. Different types of cells in our body have different jobs, which are controlled by specific genes that are only turned on in that type of cell. While we know a lot about the genes that make proteins, it's harder to identify the lncRNAs that are specific to each cell type. In this project, we will use an analysis method we developed to discover which lncRNAs are selectively expressed in different cell types. This information is important because it can help us understand the possible functions and role of lncRNAs in the body. In the next part of the project, we will focus on lncRNAs that we identified as mainly expressed in endothelial cells. These cells, which line the inside of blood vessels, play an important role in controlling blood flow and inflammation. If they do not work properly, it can lead to cardiovascular disease. lncRNAs that are mainly expressed in endothelial cells are likely to have an important role in their function; we will investigate this by studying how the cells behave when we stop the lncRNAs from working, using model blood vessels that we make in the laboratory. Through this work, we can learn more about lncRNAs in endothelial cell function and how they might be involved in the development of cardiovascular diseases.
