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RNA sequencing of a single cell reveals new mechanisms of heart disease – ScienceDaily

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Hypertrophic cardiomyopathy is a heart disease that causes tension, swelling of the heart muscle. Due to a poor understanding of the underlying mechanisms, effective clinical treatments are not available. Patients receive general heart medication and sometimes need open heart surgery to remove excess tissue. Researchers from the Hubrecht Institute have now successfully applied a new revolutionary technology (scRNA-seq) to identify the underlying mechanisms of the disease, including especially those that cause edema. A wide range of “big data” is a treasure trove of new observations that provide insight into hypertrophic cardiomyopathy and potential new therapeutic sites. The results of this study, conducted by researchers from the group of Eva van Roy, published in the journal Cellular reports on 10th May.

The heart has to be pumped every minute of every day. In patients with hypertrophic cardiomyopathy (HCM), this pumping function is disrupted due to a defect in one of the molecules that make traction. This leads to a stress response in the muscle cells and swelling of the heart muscle to compensate for the lost function. As a result, patients may experience typical symptoms of heart disease such as shortness of breath, chest pain, and aberrant heart rhythm (arrhythmia). To date, the development of HCMP therapy is hampered by a lack of understanding of these phenomena.

Gears

Surgery on patients with HCMP to remove excess heart tissue that impedes bleeding gives researchers a unique opportunity because they can use the removed tissue to study the disease. Researchers at the Hubrecht Institute have applied a new single-cell RNA sequencing technology (scRNA-seq) to this tissue to unravel the origins of HCMP. One of the researchers, Martian Verens, explains: “Human DNA contains about 30,000 genes, in fact a catalog of 30,000 types of gears, each of which has a role in ensuring the functioning of our body. Typically, research focuses on several genes that have been identified as important after years of research. scRNA-seq technology is able to quantify the activity of all 30,000 gears simultaneously to understand their role in disease. “

A key feature that makes scRNA-seq potent is that it can look at individual cells. The human body, as well as the heart, is made up of many cell types such as muscle cells, blood cells, blood vessel cells and more. Each of the cell types has its own specialization. Verens: “The study of this tissue is similar to a photo taken in Photoshop, where a cat, a dog and a bird are fused together. You don’t know what’s going on. During our scRNA-seq analysis, the cells separate from each other so we can see what’s going on. How to divide the combined photos of a cat, a dog and a bird into separate ones ”.

Huge amount of information

Applying the technique to heart tissue after surgery has allowed researchers to systematically identify changes that occur in the heart during disease. They identified many new regulatory interactions between genes and key regulatory players. Another innovation was that the researchers recorded the swelling of the cells during their analysis, which allowed them to identify genes that cause swelling associated with the disease. This knowledge can be used to develop new drugs. The current drugs used by patients with HCMP simply make the heart work less hard, thus preventing excessive damage. Using the vast amount of information obtained from this study, it is possible to develop new drugs that really address the root causes and support heart function, more effectively reducing disease progression.

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Materials provided Gubrecht Institute. Note: Content can be edited by style and length.

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