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Reprogramming of adult stem/progenitor cells into iPSCs without reprogramming factors

机译:将成年干/祖细胞重编程为iPSC,而无需重编程因子

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Reprogramming of adult somatic cells into induced pluripotent stem cells (iPSCs) has attracted considerable attention in both the scientific and public communities. This is due to the importance of iPSCs in drug screening, disease modeling, cell transplantation therapies and regenerative medicine. A lot of efforts have been devoted to the generation of iPSCs with fewer reprogramming factors and with higher efficiencies. It has been shown that removal of reprogramming barriers increases the efficiency of iPSC generation from differentiated cells up to 90%. Interestingly, having relatively fast cell cycle kinetics, plasticity and endogenous expression of particular pluripotency regulators make adult stem/progenitor cells potentially elite cells poised to become iPSCs. Moreover, it has been demonstrated that adult stem/progenitor cells are more amenable to pluripotent reprogramming than mature cells. Accordingly, it is hypothesized that certain adult stem cells could be reprogrammed into iPSCs without overexpression of exogenous pluripotency transcription factors by only combinatorial modulation of barriers and enhancers and relying on the endogenous expression of key reprogramming factors (e.g. Oct4, Sox2, etc.).
机译:将成人体细胞重编程为诱导性多能干细胞(iPSC)在科学界和公共界都引起了相当大的关注。这是由于iPSC在药物筛选,疾病建模,细胞移植疗法和再生医学中的重要性。已经以较少的重编程因子和较高的效率致力于iPSC的产生。已经显示,去除重编程障碍可将分化细胞产生iPSC的效率提高90%。有趣的是,具有相对快的细胞周期动力学,可塑性和特定多能性调节剂的内源性表达使成体干/祖细胞潜在地成为了成为iPSC的精英细胞。此外,已经证明,成体干/祖细胞比成熟细胞更适合多能性重编程。因此,假设仅通过屏障和增强子的组合调节并依靠关键重编程因子(例如Oct4,Sox2等)的内源表达,可以将某些成年干细胞重编程为iPSC,而不会过度表达外源多能性转录因子。

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