1023 – THE IMPORTANCE OF STEM CELL EXPANSION IN TOMORROW'S MEDICINE

UM171 activates a novel E3 ligase complex that mediates the degradation of the CoREST1 complex which includes the demethylase LSD1 and the HDAC1/2 deacetylases. We and others have previously shown the importance of histone modification in HSC biology. Using UM171 as a tool compound, we recently found that CoREST1 is the mediator of human HSC renewal and multipotentiality. CoREST1 is therefore critical for preventing HSC aging in vitro and potentially in vivo. This explains its unique potential during ex vivo expansion. Basic and clinical results will be presented at the meeting showing that chemical manipulation of human HSC by molecules acting on CoREST1 has potentials that far extend the mere expansion of these cells.