B5: The role of Runx1 in haematopoietic stem cells

Project leader: Dr. F. Buchholz 

The transcription factor Runx1 is an important gene required for definitive hematopoiesis and is frequently mutated in human AML. Deletion of Runx1 in murine adult hematopoietic cells leads to an increase of hematopoietic stem/progenitor cells in these animals but not to leukemia.

In order to identify factors that cooperate with Runx1 in the expansion of hematopoietic stem/progenitor cells we have conducted a genome-wide RNAi screen and have identified a polycomb group protein as a Runx1 cooperating factor. Depletion of this factor in Runx1 negative bone marrow cells immortalizes the cells in vitro. We plan to dissect the molecular mechanism underlying this cooperativity and investigate this cooperative event in vivo.