Mezenkimal Kök Hücrelerin Diamond Blackfan Anemisi Hastalığındaki Rolünün Aydınlatılması

Abstract

In this thesis, the molecular etiology of Diamond Blackfan Anemia is tried to be enlightened. For this purpose, bone marrow mesenchymal and hematopoietic stem cells from the patients were comparatively analyzed with healthy donors. A reduction in the proliferation rate and a delay in differentiation potential were shown on mesenchymal stem cells from the DBA patients. Transcriptomics analysis from the mesenchymal stem cells of the DBA patients indicated an inflammatory response. The ‘delayed’ osteogenesis process was supported with the finding that early and middle markers of osteogenesis were high and late markers of osteogenesis were decreased in the RPS19 patient. In the erythroid differentiation assay (CFU-E) from the bone marrow mononuclear cells, only one patient’s sample formed colonies. When transcriptomics analysis was examined, a change in the expression levels of the genes associated with inflammation and immune system was observed. Immunophenotyping assay showed a decrease in the proerythroblast cell numbers of the RPS19 patient and an alteration in the expression levels of genes that coordinate mRNA regulation, RNA processing and ribosome biogenesis was observed in the transcriptomics analysis. Especially a reduction in genes, that code small subunit proteins draw attention. Outputs of this thesis will be beneficial not only for DBA, but also for other bone marrow failure syndromes. In addition, omics data obtained from other ribosomopathy disorders will be important in order to enlighten the critical mechanisms such as cancer, differentiation and immune regulation.