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master's thesis
Genski izražaj dejodinaze tipa 2 u karcinomskim fibroblastima na jednostaničnoj rezoluciji
Osijek: Josip Juraj Strossmayer University of Osijek, Faculty of Medicine Osijek, 2023. urn:nbn:hr:152:342000
Stipetić, Mariela
Josip Juraj Strossmayer University of Osijek
Faculty of Medicine Osijek

Institutional repository: Repository of the Faculty of Medicine Osijek

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Stipetić, M. (2023). Genski izražaj dejodinaze tipa 2 u karcinomskim fibroblastima na jednostaničnoj rezoluciji (Master's thesis). Osijek: Josip Juraj Strossmayer University of Osijek, Faculty of Medicine Osijek. Retrieved from https://urn.nsk.hr/urn:nbn:hr:152:342000

Stipetić, Mariela. "Genski izražaj dejodinaze tipa 2 u karcinomskim fibroblastima na jednostaničnoj rezoluciji." Master's thesis, Josip Juraj Strossmayer University of Osijek, Faculty of Medicine Osijek, 2023. https://urn.nsk.hr/urn:nbn:hr:152:342000

Stipetić, Mariela. "Genski izražaj dejodinaze tipa 2 u karcinomskim fibroblastima na jednostaničnoj rezoluciji." Master's thesis, Josip Juraj Strossmayer University of Osijek, Faculty of Medicine Osijek, 2023. https://urn.nsk.hr/urn:nbn:hr:152:342000

Stipetić, M. (2023). 'Genski izražaj dejodinaze tipa 2 u karcinomskim fibroblastima na jednostaničnoj rezoluciji', Master's thesis, Josip Juraj Strossmayer University of Osijek, Faculty of Medicine Osijek, accessed 25 November 2024, https://urn.nsk.hr/urn:nbn:hr:152:342000

Stipetić M. Genski izražaj dejodinaze tipa 2 u karcinomskim fibroblastima na jednostaničnoj rezoluciji [Master's thesis]. Osijek: Josip Juraj Strossmayer University of Osijek, Faculty of Medicine Osijek; 2023 [cited 2024 November 25] Available at: https://urn.nsk.hr/urn:nbn:hr:152:342000

M. Stipetić, "Genski izražaj dejodinaze tipa 2 u karcinomskim fibroblastima na jednostaničnoj rezoluciji", Master's thesis, Josip Juraj Strossmayer University of Osijek, Faculty of Medicine Osijek, Osijek, 2023. Available at: https://urn.nsk.hr/urn:nbn:hr:152:342000

Metadata
TitleGenski izražaj dejodinaze tipa 2 u karcinomskim fibroblastima na jednostaničnoj rezoluciji
Title (english)Type 2 deiodinase gene expression in cancer-associated fibroblasts at single-cell resolution
AuthorMariela Stipetić
MentorMario Štefanić (mentor)
Committee memberStana Tokić (predsjednik povjerenstva)
Committee memberMartina Mihalj (član povjerenstva)
Committee memberMario Štefanić (član povjerenstva)
GranterJosip Juraj Strossmayer University of Osijek
Faculty of Medicine Osijek
Osijek
Defense date and country2023-09-20, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Abstract
Cilj istraživanja: Dejodinaza tipa 2 (DIO2) posreduje lokalnu konverziju tiroksina u trijodtironin u stromalnom odjeljku, ali aktivnost DIO2 u tumorskoj stromi nije poznata. U tu svrhu, ispitali smo genski izražaj DIO2 u karcinomskim fibroblastima (CAF) na jednostaničnoj rezoluciji. Nacrt studije: Jednostanični transkriptomski atlas. Materijali i metode: Konstruirali smo stanični atlas CAF visoke rezolucije koristeći javno dostupne podatke sekvenciranja jednostanične RNK za dva tumora, duktalni adenokarcinom gušterače i nemikrocelularni karcinom pluća (NSCLC, Seurat v4 protokol, Harmony algoritam). Nakon identifikacije razlikovno izraženih gena (Wilcoxonov test), provedena je ko-ekspresijska analiza i analiza obogaćenih putova (Broad Molecular Signatures Database v7.51). Rezultati: Ukupno je profilirano 3 900 visokokvalitetnih stanica, među kojima je identificirano 7 vrlo različitih vrsta CAF. Ekspresija DIO2 uglavnom je ograničena na WNT5A+MMP11+ CAF u NSCLC, čije su glavno obilježje katabolički fenotip, biljezi muralnih stanica i izražaj gena interferonskog odgovora. Nadalje, rastući izražaj DIO2 u WNT5A+MMP11+ CAF snažno je povezan s transkripcijskim značajkama invazivnih i uznapredovalih tumora. Zaključak: Rezultati nude kratki uvid u biologiju DIO2+ CAF, pružajući putokaz za razumijevanje staničnih i međuorganskih razlika u aktivnosti DIO2 unutar tumorskog okružja. Neovisna potvrda komplementarnim tehnikama nužna je za validaciju preliminarnih rezultata.
Abstract (english)
Objectives: Type 2 deiodinase boosts local conversion of thyroxine to triiodothyronine in stromal compartment, but the activity of DIO2 in tumor-associated stroma remains unknown. To this purpose, we examined the gene expression of DIO2 in cancer-associated fibroblasts at single-cell resolution. Study design: Single-cell transcriptomic atlas. Material and methods: We constructed a high-resolution cellular atlas of CAFs using publicly available single-cell RNA sequencing data for two tumors, pancreatic ductal adenocarcinoma and non-small cell lung cancer (NSCLC Seurat v4 pipeline, Harmony algorithm). The Wilcoxon test was used to identify differentially expressed genes, followed by pathway enrichment profiling (Broad Molecular Signatures Database v7.51) and coexpression analysis. Results: In total, 3 900 high-quality cells were profiled, identifying 7 highly diverse CAF types. DIO2 expression was restricted mostly to WNT5A+MMP11+ CAFs from NSCLC, which were characterized by a catabolic phenotype, mural cell markers, and expression of interferon response genes. In addition, increased DIO2 gene expression in WNT5A+MMP11+ CAFs was robustly associated with transcriptional markers of invasive and advanced tumors. Conclusion: The results offer a glimpse into the biology of DIO2+ CAFs, providing a roadmap for understanding cell-type and organ-specific differences in DIO2 activity across the tumor environment. Independent confirmation by complementary techniques is necessary to validate the preliminary results.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:152:342000
Study programmeTitle: University graduate study
Study programme type: university
Study level: graduate
Academic / professional title: magistar/magistra medicinsko laboratorijske dijagnostike (magistar/magistra medicinsko laboratorijske dijagnostike)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2024-09-24 12:18:01