线粒体的pyruvate载体通过糖溶性-表观遗传重编程来控制气道的基本原生细胞功能
Yawen Li1, Yalin He1, Qi Zheng2
1Key Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Cell stem cell
|October 19, 2024
概括
线粒体酸盐载体 (MPCs) 对气管基底细胞 (BC) 命运至关重要. 抑制MPCs允许BC扩张,并表明向酸盐-酸盐代谢可能治疗肺部疾病.
科学领域:
- 细胞生物学 细胞生物学
- 代谢调节 代谢调节 代谢调节
- 呼吸系统医学 呼吸系统医学
背景情况:
- 基底细胞 (BCs) 保持气管上皮的完整性.
- 对于气道健康和再生而言,BC命运决定至关重要.
- 功能障碍的BCs有助于COPD等肺部疾病.
研究的目的:
- 为了研究线粒体中酸盐载体 (MPC) 在基底细胞 (BC) 宿命中的作用.
- 探索控制BC分化的代谢-表观遗传联系.
- 确定涉及BC功能障碍的肺部疾病的潜在治疗点.
主要方法:
- 在小鼠和人类的BCs中抑制线粒体酸盐载体 (MPCs).
- 在小鼠中对Mpc2的遗传失活化,以研究平衡和伤害反应.
- 代谢途径的分析,包括糖解和乙-CoA生成.
- 评估与BC分化相关的表观遗传修饰和基因转录.
- 对调节酸盐-酸盐轴对BC行为影响的评估.
主要成果:
- 线粒体的酸盐载体 (MPC) 作为BC命运的必不可少的代谢检查点.
- 抑制MPC可以使小鼠和人类BCs的长期扩张.
- 在小鼠中Mpc2的失活会导致BC增生,再生受损和中间细胞的积累.
- MPC2将糖解与依赖ACLY的乙-CoA产生联系起来,这对于表观遗传控制差异化至关重要.
- 准代谢-表观遗传轴部分拯救了BCs中的YAP功能障碍表型.
- 外源酸盐促进BCs与COPD患者的分化.
结论:
- 由MPCs调节的酸盐代谢对于基底细胞 (BC) 命运决定至关重要.
- 涉及MPC2,ACLY和乙-CoA的代谢-表观遗传轴是BC差异化的关键.
- 准酸盐-酸盐代谢提供了一个潜在的治疗策略,用于纠正肺部疾病中的异常BC行为.
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