mTORC2通过ATF5介导的途径协调单细胞和颗粒细胞谱系的承诺
Yang Zhao1,2, Chenxu Zhao1,3,4, Han Guo1,3,2
1State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
iScience
|August 31, 2023
概括
里克托 deletion 损害了骨髓原体的增殖和单细胞的发展,破坏了免疫的平衡. 这项研究揭示了Rictor的Rictor.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
背景情况:
- 骨髓细胞造血对于天生的免疫恒温至关重要.
- 粒细胞巨原体 (GMPs) 和常见骨髓原体 (CMPs) 是关键的干细胞.
- 拉巴胺素复合体2 (mTORC2) 途径在血液形成中的作用的机械标正在研究中.
研究的目的:
- 研究mTORC2的一个组成部分Rictor在骨髓原体发育和免疫细胞分化中的作用.
- 阐明Rictor影响单细胞和中性粒细胞血统承诺的分子机制.
主要方法:
- 使用Rictor删除的小鼠模型.
- 通过Rictor删除的GMP和CMP进行了收养转移实验.
- 进行了殖民地形成试验,以评估祖先分化.
- 我们分析了AKT-Foxo4-ATF5-mtUPR信号通路.
主要成果:
- 里克托删除显著减少了GMP,单细胞和巨细胞,但没有影响中性粒细胞.
- 里克托被删除的原始体的收养转移显示单细胞复合受损.
- 里克托缺乏症抑制了CMP/GMP增殖和Ly6C+单细胞分化,同时增强了中性粒细胞分化.
- 过度表达ATF5或乙基化物治疗挽救了单细胞分化缺陷.
结论:
- 里克托对CMP/GMP的增殖和单细胞的正常发育至关重要.
- 里克托作为一个关键的调节器,平衡单细胞和粒细胞谱系的承诺.
- mTORC2-AKT-Foxo4-ATF5-mtUPR通路对于单细胞分化至关重要.
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