短C端木沙希-1蛋白调节胚胎干细胞中的多能状态
Youwei Chen1, Ying Chen2, Qianyan Li2
1Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China; Clinical Center for Brain and Spinal Cord Research, Medical School, Tongji University, Shanghai, China.
Cell reports
|October 20, 2023
概括
短的Musashi-1 (MSI1-C) 蛋白质对于早期胚胎发育和干细胞多能性至关重要. 它们的缺席会导致发育停止,而它们的存在会增强干细胞多能性和存活率.
科学领域:
- 发展生物学 发展生物学
- 干细胞生物学 干细胞生物学
- 分子生物学分子生物学
背景情况:
- 已知RNA结合蛋白Musashi-1 (MSI1) 能够调节成年干细胞的增殖和分化.
- 在胚胎干细胞 (ESC) 和早期胚胎发育中MSI1的特定功能尚不清楚.
研究的目的:
- 研究MSI1及其C端变体 (MSI1-C) 在小鼠和人类ESC和早期胚胎发育中的作用.
- 阐明MSI1-C影响多能性和胚胎发育的机制.
主要方法:
- 对小鼠胚胎和ESC以及人类ESC中MSI1和MSI1-C蛋白质表达的分析.
- 在小鼠模型中遗传删除MSI1和MSI1-C.
- 评估多能性标志物和发展结果.
- 研究MSI1-CRNA结合标和细胞功能,如DNA损伤修复和物种间细胞竞争.
主要成果:
- 短的MSI1-C蛋白在早期小鼠胚胎和小鼠ESC中存在,但在人类ESC中并不典型.
- 删除MSI1-C与全长MSI1一起导致胚胎发育停止和小鼠多能性丧失.
- MSI1-C是在天真多能性诱导过程中诱导的,并促进人类ESC中天真多能性获取.
- MSI1-C定位在核中,与参与DNA损伤修复的RNAs (MLH1,BRCA1,MSH2) 结合,增强人类在物种间竞争中的ESC生存率,并延长状体的形成.
结论:
- MSI1-C是ESC多能状态和早期胚胎发育的重要调节者.
- MSI1-C在维持多能性和促进发育进展方面发挥着至关重要的作用.
- 通过与DNA损伤修复通路的相互作用,MSI1-C有助于干细胞的弹性和发育潜力.
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