Laboratory of Molecular Stem Cell Biology (Rosenbauer Lab)
The main interest of our laboratory is to understand how lineage-specific transcription factors act in concert with epigenetic mechanisms to direct hematopoietic stem cell functions, such as self-renewal and differentiation, how they program precursors to adopt a certain lineage choice, how they control the development and activity of innate immune cells and how their dysregulation leads to transformation into cancer (stem) cells. We combine state-of-the-art next generation sequencing technologies with transgenic and knockout mouse models to uncover the mechanisms of how transcription factors control their target genes and how their own expression is regulated. A research focus of our laboratory is on the Ets-family transcription factor PU.1. PU.1 is essential for the development of both myeloid and lymphoid lineages; PU.1 knockout mice exhibit early lethality and lack of B-lymphocytes and mature myeloid cells. In addition, PU.1 is important for the self-renewal and differentiation of hematopoietic stem cells. We could reveal that graded changes in PU.1 concentrations have drastic effects on both lineage fate decisions and leukemic transformation. Moreover, we could decipher how PU.1 shapes the epigenome of innate immune cells in order to control their differentiation and guarantee their appropriate function. Hence, a further understanding of PU.1 will continue to unravel regulatory principles underlying normal hematopoiesis and leukemogenesis.