A novel level of regulation of normal and leukemic stem cell hierarchies by differential polyad-enylation of key transcripts (B04)

位于造血系统顶部的自我更新造血干细胞（HSC）对于成熟细胞的连续生成至关重要，并且对于响应感染，炎症或化疗等损伤线索的修复也至关重要。此外，多能造血干细胞是白血病的起源细胞，白血病干细胞可能是最初成功治疗后复发的原因。干细胞的层次结构是由一系列复杂的表观遗传机制形成的，包括差异甲基化、染色质活性、转录、翻译以及转录后和翻译后调控。在这里，我们解决的作用，差异多聚腺苷酸化的成绩单影响稳定性和蛋白质表达在正常的造血干细胞和祖细胞，并探讨这种机制是否也在白血病干细胞和耐药白血病克隆操作。

Self-renewing hematopoietic stem cells (HSCs) located atop of the hematopoietic system are crucial for the continuous generation of mature cells and also critical for repair in response to injury cues such as infection, inflammation or chemotherapy. Moreover, multipotent HSCs are the cell-of-origin of leu-kemias and leukemic stem cells are likely responsible for relapse after initially successful therapy. Stem cell hierarchies are shaped by a complex array of epigenetic mechanisms including differential methylation, chromatin activity, transcription, translation as well as post-transcriptional and post-translational regulation. Here we address the role of differential polyadenylation of transcripts affecting stability and protein expression in normal HSCs and progenitors and explore whether this mechanism is also operational in leukemic stem cells and therapy resistant leukemic clones.