Doctoral defence: Ihor Filippov „Single-cell data analysis in immunology: from technology to applications“

On May 28 at 14:00 Ihor Filippov will defend his medicine doctoral thesis „Single-cell data analysis in immunology: from technology to applications“.

Supervisor:
Professor Pärt Peterson, University of Tartu

Oponent:
Associate Professor Nuno Luis Barbosa Morais, University of Lisbon (Portugal)

Kokkuvõte

Single-cell RNA sequencing (scRNA-seq) is a technology that enables the study of cellular heterogeneity at the individual cell level. This method allows for the observation of gene expression in millions of cells and the identification of rare cell types and the molecular mechanisms occurring within them.

In this thesis, the suitability of different scRNA-seq solutions for studying immune cells was assessed. The thymus, a complex primary immune organ in terms of cellular composition, was used as the source material. A comparison of two scRNA-seq methods revealed significant differences, and the analysis highlighted both the strengths and weaknesses of the methods used in immune organ analysis.

A second focus of the thesis was the investigation of immune cells in the context of the monogenic disease APS-1 (autoimmune polyendocrinopathy syndrome type 1). APS-1 is caused by mutations in the AIRE gene, leading to impaired immune tolerance, which results in the development of autoreactive T cells and autoimmune diseases. In this study, scRNA-seq technology was employed to analyze transcriptomic changes in the regulatory T cells of APS-1 patients, which play a role in the establishment of immune tolerance.

Thirdly, age-related changes in the immune system were examined. Aging is characterized by chronic inflammation and a weakened ability to respond to viruses and other pathogens. Additionally, chronic viral infections, such as cytomegalovirus (CMV) infection, exacerbate age-related immune changes. This study identified a decline in the population of CD8 naïve T cells in the peripheral blood mononuclear cells of elderly individuals, characterized by the upregulation of inflammatory genes. Furthermore, CMV infection- and aging-related subtypes of CD8+ Temra cells were mapped.

The findings of this dissertation demonstrate the advantages of scRNA-seq technology in studying complex cellular systems, contributing to the characterization of immune cells and a deeper understanding of their functions.

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