外环境因素对体细胞重编程诱导多能干细胞的影响

Microenvironmental cues influence the reprogramming of somatic cells to induced pluripotent stem cells

背景:诱导多能干细胞具有广阔的应用前景,转录因子介导的细胞重编程效率较低,不利于多能干细胞的临床应用。近年来研究发现多种微环境因素对细胞重编程有显著影响,能够有效提高重编程效率,对这些因素的总结和归纳有利于建立适合细胞重编程的培养环境,促进该技术的广泛应用。目的:对有利于多能干细胞干性维持和提高细胞重编程效率的微环境因素进行归纳总结。方法:由第一作者检索Web of Science数据库2006年至今有关外环境理化因素对多能干细胞干性维持和细胞重编程影响的文章,从中挑选80篇与研究目的相关性较强,质量较高的文章进行总结。结果与结论:细胞与基质材料的黏附以及细胞间黏附不仅调控细胞的基因表达,还通过肌动蛋白骨架与核膜直接连接,影响细胞的表观遗传状态,因而可以调控细胞重编程。此外低氧、动态培养和电信号等因素也能够影响重编程效率。

BACKGROUND:Induced pluripotent stem cells hold enormous potential as a tool to generate cells for disease therapy and modeling.However,the lower efficiency of cell reprogramming using exogenous transcription factors limits the clinical use of induced pluripotent stem cells.Recent studies have indicated that microenvironmental cues can promote the production of pluripotent cells.Further summarization on these reports will provide new strategies to enhance the safety and efficiency of the reprogramming technology.OBJECTIVE:To summarize the effect of microenvironmental cues on the reprogramming of somatic cells to induced pluripotent stem cells and the maintenance of pluripotency.METHODS:Scientific papers from 2006 to present included in Web of Science were searched by the first author.Eighty papers focusing on the effect of microenvironmental cues on the reprogramming of somatic cells to induced pluripotent stem cells and the maintenance of pluripotency were included.RESULTS AND CONCLUSION:Cell-matrix interaction and cell-cell adhesion regulate gene expression and have effects on the epigenetic states of the chromatin through a direct connection between actin cytoskeletons and the nuclear membrane;thus,manipulation of the cell-matrix interaction and cell-cell adhesion can improve the induction of pluripotency.In addition,other environmental factors including hypoxia,dynamic culture and electrical stimulation can also promote cell reprogramming.