整合素和E-钙黏素在诱导多能干细胞重编程及干性维持中的作用

The roles of integrins and E-cadherin in the reprogramming and stemness maintenance of induced pluripotent stem cells

背景:诱导多能干细胞在疾病模型和再生医学领域具有广阔的应用前景,能够利用安全高效的方法进行体细胞重编程是诱导多能干细胞广泛应用于临床的前提。近年来研究者们发现细胞黏附分子整合素和E-钙黏素对诱导多能干细胞重编程和干性维持有重要影响,对其分子机制的研究将帮助研究者设计更加安全有效的重编程方法和深入全面的理解重编程过程。目的:从机制层面对整合素和E-钙黏素在诱导多能干细胞重编程及干性维持中的作用进行归纳总结。方法:由第一作者检索Web of Science数据库2006年至今有关细胞黏附影响诱导多能干细胞重编程及干性维持的文献,从中挑选63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:整合素介导的细胞-基质间黏附与E-钙黏素介导的细胞-细胞间黏附可分别激活下游信号通路调控多能性基因表达,还可以作用于细胞骨架与核膜直接连接,通过多种机制产生基因水平、蛋白质水平和表观遗传学水平上的变化,最终影响诱导多能干细胞重编程及干性维持。

BACKGROUND:Induced pluripotent stem cells(iPSCs)hold enormous potential as a tool to generate cells for disease modeling and regenerative medicine.The premise for clinical application of iPSCs is the efficient reprogramming of somatic cells to iPSCs.In recent years,increasing studies have demonstrated that integrins and E-cadherin play important roles in the reprogramming and maintenance of iPSCs.Investigations on the underlying molecular mechanism will help us developing safer and more efficient reprogramming methods for iPSCs generation and deeply understanding the reprogramming process.OBJECTIVE:To summarize the effect of integrins and E-cadherin on the reprogramming of iPSCs and the maintenance of pluripotency based on the insights into the underlying molecular mechanisms.METHODS:Scientific papers published from 2006 to present that described the effects of cell adhesion on reprogramming and stemness maintenance of iPSCs were retrieved by the first author in the Web of Science.Sixty-three articles related to the purpose of this review were reviewed.RESULTS AND CONCLUSION:Integrins-mediated cell-matrix adhesion and E-cadherin-mediated cell-cell adhesion can regulate pluripotent gene expression through a variety of downstream signaling pathways,and can also play important roles in the organization and contractility of actin cytoskeletons that generate gene-,protein-,and epigenetic-level changes and ultimately influence cell reprogramming and stemness maintenance.