Diabetes Transplant Unit, The Prince of Wales Hospital and University of New South Wales, Sydney, Australia.
Cell Adh Migr. 2010 Jan-Mar;4(1):39-45. doi: 10.4161/cam.4.1.10627. Epub 2010 Jan 13.
Human embryonic stem cells (hESCs) can be directed to differentiate into a number of endoderm cell types, however mature functional cells have yet to be produced in vitro. This suggests that there may be important factors that have yet to be described, which may be essential for the proper derivation of these cells. One such factor is the integrin mediated interactions between a cell and the extracellular matrix (ECM). On this basis, the present study investigated the role of the ECM in the directed differentiation of hESCs to definitive endoderm via analysis of integrin gene expression. The results showed that definitive endoderm can be efficiently and effectively derived from hESCs in a feeder free, single defined ECM of laminin. Analysis of integrin expression also showed that definitive endoderm highly express the integrins alphaV and beta5, which have the ability to bind to vitronectin, whilst expression of the pluripotency related laminin binding integrins alpha3, alpha6 and beta4 were downregulated. This suggested a potential role of vitronectin binding integrins in the development of definitive endoderm.
人类胚胎干细胞(hESCs)可以被定向分化为多种内胚层细胞类型,然而,在体外尚未产生成熟的功能细胞。这表明可能存在尚未描述的重要因素,这些因素对于这些细胞的正确分化可能是必不可少的。其中一个因素是细胞与细胞外基质(ECM)之间的整合素介导的相互作用。在此基础上,本研究通过分析整合素基因表达,研究了 ECM 在 hESC 向确定的内胚层定向分化中的作用。结果表明,在无饲养层、单一明确的层粘连蛋白 ECM 中,可以有效地从 hESC 中高效地衍生出确定的内胚层。整合素表达分析还表明,确定的内胚层高度表达能够结合 vitronectin 的整合素 alphaV 和 beta5,而与层粘连蛋白结合的多能性相关的整合素 alpha3、alpha6 和 beta4 的表达下调。这表明 vitronectin 结合整合素在确定的内胚层发育中可能具有潜在作用。