通过调节GDNF/GFRα1轴,APE1促进胚胎干细胞的增殖和瘤的形成
Ling Liu1, Qiang Wu2, Zan Wang3
1Department of Pathology, Childern's Hospital of Hebei Province, Shijiazhuang, Heibei 050031, China.
Reproductive biology
|July 31, 2023
概括
在小鼠干细胞中击败apurinic/apyrimidinic内核酶1 (APE1) 降低了增殖和多能性. 通过影响GDNF/GFRα1通路,APE1抑制也减少了瘤的形成.
科学领域:
- 干细胞生物学 干细胞生物学
- 癌症研究 癌症研究
- 分子生物学分子生物学
背景情况:
- 瘤形成是胚胎干细胞 (ESC) 临床应用的一个主要障碍.
- 阿普里尼克/阿普里米尼克内核酶1 (APE1) 涉及瘤发育和干细胞分化,但其在瘤形成中的作用尚不清楚.
研究的目的:
- 研究APE1在小鼠ESC (mESC) 增殖,多能性,分化和瘤形成中的作用和机制.
主要方法:
- 反转录定量聚合酶连锁反应 (RT-qPCR) 和西部涂抹来评估APE1的表达.
- 细胞计数,流细胞计量和西部斑检测用于评估增殖,细胞周期和多能性标记物.
- 异种移植的小鼠模型用于研究瘤的形成.
主要成果:
- 在mESC分化过程中,APE1表达增加.
- APE1的敲击降低了mESC的扩散,诱导了G2/M阶段停止,并降低了多能性标志物.
- 在活体中,APE1抑制抑制了瘤体积和改变了外皮/内皮标志物表达.
- 在机制上,APE1调节GDNF和GFRα1,它们调节其对多能性和胚胎生成的影响.
结论:
- APE1在mESC的增殖,多能性和胚胎生成中发挥着关键作用.
- 下调APE1通过GDNF/GFRα1信号通路减弱mESC多能性和瘤形成.
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