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METHOD FOR EXPANDING STEMNESS AND DIFFERENTIATION POTENTIAL OF PLURIPOTENT CELLS

机译:扩大多能细胞的干细胞和分化潜能的方法

摘要

Method for expanding stemness and differentiation potential of pluripotent cells. The invention is based on the finding that increasing micro RNA-203 levels in induced pluripotent stem (iPSCs) or embryonic stem (ESCs) cells improves the quality cell fate potential and ability of these cells to differentiate into multiple cell lineages and to reach further maturation properties without interfering with their self-renewal properties. This effect is mediated through the mi R-203-dependent control of de novo DNA methyltransferases Dnmt3a and Dnmt3b, which in turn regulate the methylation landscape of pluripotent cells. The effect can be achieved by overexpression of micro RNA-203 or by adding micro RNA-203 or analogues thereof to the cell culture medium and can be observed using a variety of cellular and in vivo models. The generated cells are naïve pluripotent cells with an improved capacity to differentiate, that can be used to obtain more efficiently differentiated and mature cells proficient for regerative medicine strategies.
机译:扩展多能细胞干和分化潜能的方法。本发明基于以下发现:在诱导多能干(iPSC)或胚胎干(ESC)细胞中增加微小RNA-203的水平可改善细胞命运的潜力以及这些细胞分化为多种细胞谱系并达到进一步成熟的能力。属性,而不会影响其自我更新属性。这种作用是通过 de novo DNA甲基转移酶Dnmt3a和Dnmt3b的mi R-203依赖性控制来介导的,它们反过来又调节了多能细胞的甲基化态势。该效果可以通过微RNA-203的过表达或通过向细胞培养基中添加微RNA-203或其类似物来实现,并且可以使用多种细胞和体内模型观察到。产生的细胞是具有提高的分化能力的幼稚多能细胞,可用于获得更有效的分化细胞和成熟的细胞,这些细胞熟练用于重症医学策略。

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