循环拉伸促进细胞重编程过程通过细胞骨-核机械合和表观遗传修饰
Sung-Min Park1,2, Jung-Hwan Lee1,2,3,4,5,6,7, Kwang Sung Ahn1,2
1Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|September 20, 2023
概括
纤维细胞的循环拉伸通过激活机械转导和表观遗传变化来增强诱导的多能干细胞 (iPSC) 生产. 这种物理力方法改善了用于再生医学和疾病建模的细胞重编程.
科学领域:
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
- 再生医学是一种再生医学.
背景情况:
- 细胞重编程对于再生疗法,疾病建模和药物发现至关重要.
- 生物物理线索影响细胞命运,但外部物理力量在重编程中的作用尚未完全理解.
研究的目的:
- 研究时间循环拉伸对诱导多能干细胞 (iPSC) 生产效率的影响.
- 阐明涉及拉伸增强重编程的潜在机械转导和表观遗传机制.
主要方法:
- 纤维细胞受到时间循环拉伸.
- 诱导多能干细胞 (iPSC) 的生成和表征 (多能性标志物,体内功能).
- 大量和单细胞RNA测序,全基因组ChIP测序和药理抑制被用于分析分子和表观遗传变化.
主要成果:
- 循环拉伸显著提高了iPSC生产效率.
- 伸展的iPSC表达了多能性标志物,并显示了体内功能.
- 机制包括增加细胞分裂,介质细胞-上皮细胞过渡,机械敏感分子 (整合素,YAP) 的激活和表观遗传修饰 (H3K9甲基化下调).
结论:
- 时间循环拉伸是一种强大的物理刺激,通过机械转导和表观遗传改变增强细胞重编程.
- 这项研究建立了物理力,机械传导,表观遗传变化和iPSC生成中的基因表达之间的联系.
- 这些发现对细胞生物学,组织工程和再生医学的进步有重大影响.
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