Notch in hematopoietic stem cell differentiation and leukaemia development
The relevance of adult (somatic) stem cell research is increasing steeply with a growing number of human diseases shown to be curable by stem cell therapy. The present study plan aims the research towards the gene regulatory mechanisms that control hematopoietic stem cell (HSCs) homeostasis and differentiation, which is tightly regulated by an interplay of a number of transcription factors and environmental signals mediated by a Notch signaling pathway. Our group designed an experimental approach for studying the interaction of Notch signaling pathway with transcription factor genes associated with hematopoiesis with focus on Ikaros gene family. Our laboratory has established a diagnostic technique for quick and sensitive detection of aberrant Notch and Ikaros forms by single cell multiplex qRT-PCR, which is a unique tool enabling us to dissect the contribution of different members of the Ikaros and Notch families on differentiation and survival of hematopoietic cells in a context of regulation of expression of target genes as well as non-coding RNAs, since they maintain the spatial organization of chromosome structure and regulate cell commitment. Our results will improve diagnosis and risk stratification for leukaemia patients which will be an important aid in informed clinical decisions. Therefore the proposed project will substantially advance the field towards better therapeutic options and contribute significantly to the field of stem cell medicine.