亚酸盐调节血造干细胞功能和白血病发生
Michalis Agathocleous1, Corbin E Meacham1, Rebecca J Burgess1
1Children's Research Institute and the Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Nature
|August 22, 2017
概括
代谢物水平的生理变化调节干细胞功能. 血造干细胞 (HSC) 中的高酸盐水平限制了它们的频率和功能,而耗尽则加速白血病.
科学领域:
- 生物化学
- 细胞生物学
- 血液学
背景情况:
- 干细胞命运受到培养中的代谢物的影响.
- 通过体内生理代谢物变化的干细胞功能调节尚不清楚.
研究的目的:
- 研究生理代谢物变异在体内干细胞功能的作用.
- 开发一种直接从组织中分析罕见细胞群的代谢学方法.
主要方法:
- 开发了一种用于罕见细胞群体分析的新型代谢学方法.
- 鼠标造血干细胞 (HSC) 和前代细胞的代谢特征比较.
- 研究了系统性酸盐耗尽对小鼠的HSC的影响.
主要成果:
- 对于每个造血细胞类型,都确定了不同的代谢特征.
- 在HSC中,酸盐含量很高,随着分化而下降.
- 亚酸盐消耗增加了HSC的频率和功能,部分原因是抑制了瘤抑制剂Tet2.
- 亚酸盐的消耗加速了Flt3突变的白血病发生,这种效应被食亚酸盐逆转.
结论:
- 在HSC积累促进Tet活动,限制HSC频率和抑制白血病发生.
- 亚酸盐通过Tet2依赖和独立的机制负面调节HSC功能和骨髓形成.
- 代谢物水平,特别是酸盐,在调节干细胞功能和预防体内白血病方面发挥着至关重要的作用.
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