Transcription factors regulating normal and pathological platelet differentiation

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To understand the molecular mechanism for platelet production from hematopoietic stem cells, we focused on the Runx1 gene, which is closely related to familial platelet disorder (FPD). In the current study, RUNX1 is shown to bind to the promoter sequence of the PF4 gene, which is expressed only in platelet lineage, and cooperatively activate the promoter with ETS family proteins, ETS-1 and FLI-1. On the other hand, RUNX1 mutants found in the FPD patients could not activate the promoter. To understand the functional difference between wild type and mutant RUNX1 in physiological platelet differentiation, a novel ES cell differentiation system was established, in which exogenous genes can be overexpressed only in platelet lineage