PTEN通过PU.1-依赖的染色质可访问性来调节造血系的可塑性
Zihan Xu1, Libing He2, Yilin Wu2
1The MOE Key Laboratory of Cell Proliferation and Differentiation, Center for Bioinformatics, School of Life Sciences, Peking University, Beijing, China; Center for Statistical Science, Peking University, Beijing, China.
Cell reports
|August 10, 2023
概括
在造血干细胞 (HSC) 中的PTEN损失通过改变细胞发育驱动白血病. 一个关键的转录因子PU.1,可以重新编程这些细胞,提供新的治疗点.
科学领域:
- 血液形成 血液形成 血液形成
- 癌症生物学 癌症生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 造血干细胞 (HSC) 中的PTEN损失与改变的血统潜力和T细胞急性淋巴细胞白血病 (T-ALL) 有关.
- 了解PTEN调节血统承诺的精确机制对于白血病研究至关重要.
研究的目的:
- 调查PTEN损失影响血液生成系选择的分子机制.
- 为了确定关键的发育阶段和转录因子涉及PTEN介导的血统可塑性.
主要方法:
- 从小鼠前白血病HSC获得的ATAC-seq和单细胞RNA-seq数据的综合分析.
- 在体外培养实验中,使用Pten-null预先B细胞进行培养.
- 功能性研究涉及操纵PU.1水平.
主要成果:
- 在前B细胞阶段,PTEN损失改变了在临界转录因子结合部位的染色质可访问性.
- 这种表观遗传重编程导致骨髓和T细胞潜力增加,B细胞潜力降低.
- PU.1 作为PTEN的关键下游效应因子,能够在Pten-null细胞中重新编程染色质可访问性和谱系潜力.
结论:
- 前B细胞阶段是PTEN调节的造血系决定的关键窗口.
- PU.1在调节前亲B祖先的表观遗传景观和血统可塑性方面发挥着关键作用,这表明它在T-ALL发育中的重要性.
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