报告题目🐷：Runx1 Deficiency Decreases Ribosome Biogenesis and Confers Stress Resistance to Hematopoietic Stem and Progenitor Cells.

报告人👨🏻‍🎓🤥：蔡雄伟 博士

主持人：李大力 研究员

报告时间：2016年4月14日13:00

报告人简介🕜：蔡雄伟💇🏻‍♂️，2007年从中国医学科天美／北京协和医天美肿瘤研究所博士毕业。于2008年加入Nancy Speck博士实验室，以条件敲除小鼠模型💪🏿，研究转录因子Runx1对造血干细胞和白血病发生的作用，并且根据作用的分子机制寻找有效的治疗靶点。

 

报告摘要：The transcription factor RUNX1 is frequently mutated in myelodysplastic syndrome and leukemia. Runx1 mutations were an independent prognostic marker, which was correlated with poor prognosis. RUNX1 mutations can be early events, creating preleukemic stem cells that expand in the bone marrow. Here we show, counterintuitively, that Runx1-deficient hematopoietic stem and progenitor cells (HSPCs) have a slow growth, low biosynthetic, small cell phenotype and markedly reduced ribosome biogenesis (Ribi). The reduced Ribi involved decreased levels of rRNA and many mRNAs encoding ribosome proteins. Runx1 appears to directly regulate Ribi; Runx1 is enriched on the promoters of genes encoding ribosome proteins and binds the rDNA repeats. Runx1-deficient HSPCs have lower p53 levels, reduced apoptosis, an attenuated unfolded protein response, and accordingly are resistant to genotoxic and ER stress. The low biosynthetic activity and corresponding stress resistance provides a selective advantage to Runx1-deficient HSPCs, allowing them to expand in the bone marrow and outcompete normal HSPCs.