In a recent study, researchers at the Medical University of Vienna have investigated the cellular and molecular basis of idiopathic subglottic tracheal stenosis (ISGS) and identified specific cells that contribute to disease development. ISGS is a rare disease which mainly affects women and leads to a narrowing of the upper trachea due to scar formation. This disease manifests itself in symptoms such as whistling breath sounds and possible voice changes, but can also lead to serious respiratory distress.
In order to identify the previously unknown pathological aspects of ISGS, the research team led by first author Martin Direder (Department of Orthopedics and Trauma-Surgery) and study leaders Hendrik J. Ankersmit (Department of Thoracic Surgery) and Michael Mildner (Department of Dermatology) used single-cell RNA sequencing (scRNAseq). This innovative method enables a detailed analysis of the cell types and their gene expression in the tissue and thus allows a precise picture of the cellular composition of fibrotic tissue to be drawn. Fibrosis refers to the pathological proliferation of connective tissue or excessive scarring that can occur in various organs.
The analysis revealed that the fibrotic tissue of ISGS contains a specific subset of fibroblasts - cells responsible for the formation of scar tissue - as well as Schwann cells in an activated state. Schwann cells normally play an important role in nerve function and support nerve regeneration after injury. These cells showed a specific gene expression pattern indicating their involvement in matrix formation. The involvement of Schwann cells in scar formation and fibrotic processes was recently described by the research group for the first time in the skin. The present study therefore confirms the previous hypothesis that Schwann cells can play an important role in fibrotic diseases of various organs. In addition, an increased number of plasma cells, which are responsible for the production of antibodies, was found. Plasma cells that were concentrated in specific areas of fibrotic tissue showed an overexpression of genes that are important for the production of immunoglobulin G (IgG). An enrichment of these cells has already been observed in other fibrotic diseases, suggesting a similar role in the development and progression of ISGS.
"The study of single-cell transcriptional profiles allows us to better understand the pathological conditions and the altered cellular environment in ISGS," says first author Martin Direder. "Our results show that ongoing fibrotic processes take place in ISGS and that fibroblasts, Schwann cells and plasma cells contribute significantly to disease development," explains co-study leader Hendrik Jan Ankersmit, "this knowledge could be crucial for the development of future diagnostic and treatment methods."
The findings of this study contribute to a better understanding of the complex mechanisms of ISGS and could form the basis for the development of targeted therapeutic approaches that modulate the pathological activity of the cell types involved.
Publication: Frontiers in Cell and Developmental Biology
Transcriptional profiling sheds light on the fibrotic aspects of idiopathic subglottic tracheal stenosis Martin Direder, Maria Laggner, Dragan Copic, Katharina Klas, Daniel Bormann, Thomas Schweiger, Konrad Hoetzenecker, Clemens Aigner, Hendrik Jan Ankersmit und Michael Mildner; Front. Cell Dev. Biol. 12:1380902DOI 10.3389/fcell.2024.1380902
