MedUni Vienna: New Cell Atlas Reveals Diseases of the Thymus
A multidisciplinary research team at the Medical University of Vienna has created a comprehensive cell atlas of the human thymus, providing new insights into the development and biological differences of rare thymus diseases and tumours.
The study, published in Nature Communications, analysed a total of 453,727 individual cells from 53 datasets and represents the first systematic comparison between healthy thymus tissue at different stages of life and pathological conditions such as thymic hyperplasia and thymic tumours. The findings provide an important foundation for a better understanding of these rare diseases and may contribute to the development of more precise diagnostic and therapeutic approaches in the future.
The thymus is a central organ of the immune system and plays a crucial role in the maturation of T cells, which are responsible for targeted immune defence. Although the organ normally regresses with age, pathological changes can occur in rare cases. These include thymic tumours, which originate from the epithelial cells of the thymus, as well as thymic hyperplasia, in which the organ remains functional but becomes enlarged.
Due to the rarity of these conditions, their molecular causes have remained poorly understood. The newly developed cell atlas now provides unprecedented insights into the biological mechanisms underlying these diseases.
“The cell atlas we have created provides, for the first time, a detailed systematic overview that will enable pathological changes in the thymus to be precisely classified in future,” explains co-study leader Hendrik Jan Ankersmit from the Department of Thoracic Surgery at MedUni Vienna.
Detailed Analysis at the Single-Cell Level
To create the atlas, the research team applied single-cell RNA sequencing, a technology that allows the gene activity of individual cells to be analysed with high precision.
The researchers identified specific alterations in thymic epithelial cells, which are essential for T-cell development, as well as in fibroblasts, connective tissue cells that help shape the structure of the organ.
The analysis also revealed two previously unknown cell populations. These specialised epithelial cells and fibroblasts were found almost exclusively in tumour tissue and were shown to activate genetic programmes associated with tissue remodelling and developmental processes.
“This newly acquired knowledge allows us to understand the biological differences between the individual tumour types much better,” says lead author Martin Direder-Scheiber from the Department of Orthopedics and Trauma Surgery at MedUni Vienna.
The study further demonstrated that different thymic tumour subtypes are driven by molecular mechanisms that are partly shared and partly distinct.
“This is an essential prerequisite for diagnosing these diseases in a more differentiated manner and treating them in a targeted way in the future,” explains co-study leader Michael Mildner from the Department of Dermatology at MedUni Vienna.
New Opportunities for Immunological Research
Thymic tumours are among the rarest forms of cancer and account for less than one percent of all malignant tumours of the chest cavity. They develop in the anterior mediastinum, the area between the lungs, and are often discovered incidentally.
The newly generated data contribute significantly to distinguishing these rare tumours from benign conditions such as thymic hyperplasia and provide a deeper understanding of their biology.
“As the thymus plays a key role in the development of the body’s immune system, our detailed insights may also open up new avenues for immunological research,” emphasises co-author Bernhard Moser from the Department of Thoracic Surgery at MedUni Vienna.
Long-Term Support for Rare Disease Research
Basic research into thymus pathology at the Department of Thoracic Surgery has been supported since 2010 through the Christian Doppler Laboratory for the Diagnosis and Regeneration of Heart and Thoracic Diseases and by APOSCIENCE AG.
“The successful cooperation between public and private interests represents an alternative to conventional funding bodies for defining medically relevant research questions in the field of rare diseases. The understanding and potential of the link between basic research and surgery were recognised in this project and have made this important publication possible,” says Hendrik Jan Ankersmit.