Finding the molecular basis for developmental-stage specific differences in hematopoietic stem and progenitor cells

While the mutation of GATA1 (GATA1 s) has no phenotypic effect on adult hematopoietic stem and progenitor cells (HSPCs) it perturbs fetal hematopoiesis causing – on the background of trisomy 21 – transient leukemia (DS-TL) in neonates. The aim of this project is to elucidate the genetic background responsible for the sensitivity of fetal HSPCs towards GATA1-mutation. From gene array data, we chose genes with known involvement in hematopoiesis and/or oncogenesis, which were highly overexpressed in fetal HSPCs as compared to their adult counterparts. We validated them by qRT-PCR and cloned shRNAs directed to these…