Transcription factors regulating normal and pathological platelet differentiation

为了了解造血干细胞产生血小板的分子机制，我们将重点放在与家族性血小板疾病（FPD）密切相关的Runx 1基因上。在目前的研究中，RUNX 1被证明与PF 4基因的启动子序列结合，该基因仅在血小板谱系中表达，并与ETS家族蛋白ETS-1和FLI-1协同激活启动子。另一方面，在FPD患者中发现的RUNX 1突变体不能激活启动子。为了了解野生型和突变型RUNX 1在生理性血小板分化中的功能差异，我们建立了一种新的ES细胞分化系统，其中外源基因只能在血小板谱系中过表达

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