Hematopoietic stem and progenitor cells (HSPC) have a very important role by maintaining the number of stem cells in the bone marrow (BM) but also giving rise to all mature blood cell types during differentiation. MicroRNAs (miRNAs, miRs), which are short, non-coding RNAs, have the ability to alter this balance between self-renewal and differentiation. Of special interest in this project was the miR-125a, a member of the miRcluster 99b/let-7e/125a which is associated with a reduced apoptosis in hematopoietic cells and a proliferative advantage by targeting pro-apoptotic and proliferation related genes. The effect of miR-125a is particularly interesting because the overexpression of this miRNA leads to a ~20-fold increased frequency of hematopoietic stem cells (HSC). This is important when thinking about BM transplantation for patients suffering from e.g. acute myeloid leukemia (AML). To further investigate the clonality of miR-125a overexpressing cells, to find out how many stem cells actually contribute to hematopoiesis, HSCs were transduced with a barcoded retroviral vector, allowing for unique labeling of each transduced cell and tracking their progeny. |