Spatial Transcriptomics of Celiac Disease Small Intestine in Different Stages of Inflammation
Siukola, Emilia (2024)
Siukola, Emilia
2024
Bioteknologian ja biolääketieteen tekniikan maisteriohjelma - Master's Programme in Biotechnology and Biomedical Engineering
Lääketieteen ja terveysteknologian tiedekunta - Faculty of Medicine and Health Technology
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Hyväksymispäivämäärä
2024-05-13
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-202404153539
https://urn.fi/URN:NBN:fi:tuni-202404153539
Tiivistelmä
Celiac disease (CeD) is a multifactorial autoimmune disease where ingestion of gluten found in barley, wheat, and rye, leads to inflammation of the small intestine. Gliadin, one of the main components of gluten, contains critical epitopes, which will induce a CD4+ T-lymphocyte response in the intestinal mucosa of CeD patients when presented by the disease-associated DQ2 molecules; either HLA-DQ2 or HLA-DQ8. While progress has been made in understanding its pathogenesis, the molecular interactions underlying celiac disease’s development are yet to be fully elucidated. Traditional transcriptomics methods often overlook the spatial context of gene expression within
tissues, potentially ignoring critical molecular interactions. Therefore, comprehensive gene expression studies with spatial context are needed. The primary aim of this thesis was to optimize the GeoMx Spatial Transcriptomics assay for small intestine samples and to evaluate whether there are differences in gene expression profiles between patient groups.
First, we optimized morphology markers to characterize tissue morphology. Then, we performed spatial transcriptomics workflow using the GeoMx Spatial Transcriptomics assay. Lastly, we analyzed and visualized the gene expression data. We compared the gene expression profiles and enriched pathways between celiac and control samples, as well as between celiac and inflammation samples. To our knowledge, this study represents the first spatial transcriptomics study for human small intestine samples. The results revealed significant differences in the gene expression profiles between control and celiac samples. Further exploration through pathway analysis elucidated the dysregulation in molecular pathways, such as interferon signaling and immune response activation, underlying CeD and inflammation. Finally, we found that there were shared molecular signatures between celiac and inflammation samples. These findings suggest that interventions targeting immune dysregulation may hold promise for individuals with a potential form of celiac disease.
To conclude, this study suggests heightened antigen presentation and immune surveillance in response to gluten-induced inflammation. Furthermore, results support the hypothesis that individuals with a potential form of celiac disease could benefit from adhering to a gluten-free diet. However, further studies with larger cohorts are needed to validate these results.
tissues, potentially ignoring critical molecular interactions. Therefore, comprehensive gene expression studies with spatial context are needed. The primary aim of this thesis was to optimize the GeoMx Spatial Transcriptomics assay for small intestine samples and to evaluate whether there are differences in gene expression profiles between patient groups.
First, we optimized morphology markers to characterize tissue morphology. Then, we performed spatial transcriptomics workflow using the GeoMx Spatial Transcriptomics assay. Lastly, we analyzed and visualized the gene expression data. We compared the gene expression profiles and enriched pathways between celiac and control samples, as well as between celiac and inflammation samples. To our knowledge, this study represents the first spatial transcriptomics study for human small intestine samples. The results revealed significant differences in the gene expression profiles between control and celiac samples. Further exploration through pathway analysis elucidated the dysregulation in molecular pathways, such as interferon signaling and immune response activation, underlying CeD and inflammation. Finally, we found that there were shared molecular signatures between celiac and inflammation samples. These findings suggest that interventions targeting immune dysregulation may hold promise for individuals with a potential form of celiac disease.
To conclude, this study suggests heightened antigen presentation and immune surveillance in response to gluten-induced inflammation. Furthermore, results support the hypothesis that individuals with a potential form of celiac disease could benefit from adhering to a gluten-free diet. However, further studies with larger cohorts are needed to validate these results.