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Plant hormones increase efficiency of reprogramming mouse somatic cells to induced pluripotent stem cells and reduce tumorigenicity

机译:植物激素可提高将小鼠体细胞重编程为诱导多能干细胞的效率,并降低致瘤性

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摘要

Reprogramming of somatic cells into induced pluripotent stem (iPS) cells by defined pluripotency and self-renewal factors has taken stem cell technology to the forefront of regenerative medicine. However, a number of challenges remain in the field including efficient protocols and the threat of cancer. Reprogramming of plant somatic cells to plant embryonic stem cells using a combination of two plant hormones was discovered in 1957 and has been a routine university laboratory practical for over 30 years. The plant hormones responsible for cell reprogramming to pluripotency, indole-3-acetic acid (IAA) and isopentenyl adenosine (IPA), are present in human cells, leading to the exciting possibility that plant hormones might reprogram mammalian cells without genetic factors. We found that plant hormones on their own could not reprogram mammalian cells but increase the efficiency of the early formation of iPS cells combined with three defined genetic factors during the first 3 weeks of reprogramming by accelerating the cell cycle and regulating pluripotency genes. Moreover, the cytokinin IPA, a known human anticancer agent, reduced the threat of cancer of iPS cell in vitro by regulating key cancer and stem cell-related genes, most notably c-Myc and Igf-1. In conclusion, the plant hormones, auxin and cytokinin, are new small chemicals useful for enhancing early reprogramming efficiency of mammalian cells and reducing the threat of cancer from iPS cells. These findings suggest a novel role for plant hormones in the biology of mammalian cell plasticity
机译:通过定义的多能性和自我更新因子将体细胞重编程为诱导性多能干(iPS)细胞,已将干细胞技术带入了再生医学的前沿。但是,该领域仍然存在许多挑战,包括有效的方案和癌症的威胁。使用两种植物激素的组合将植物体细胞重编程为植物胚胎干细胞是在1957年发现的,并且已经在30多年的实践中作为大学的常规实验室。人体细胞中存在负责将细胞重编程为多能性的植物激素,吲哚-3-乙酸(IAA)和异戊烯基腺苷(IPA),这导致了令人激动的可能性,即植物激素可能会在没有遗传因素的情况下对哺乳动物细胞进行重编程。我们发现,植物激素本身不能重编程哺乳动物细胞,但可以通过加快细胞周期和调节多能性基因,在重编程的前3周内提高iPS细胞与三种定义的遗传因子结合的早期形成的效率。此外,细胞分裂素IPA(一种已知的人类抗癌药)通过调节关键的癌症和与干细胞相关的基因(最著名的是c-Myc和Igf-1)来降低iPS细胞在体外的癌症威胁。总之,植物激素,生长素和细胞分裂素是新的小型化学品,可用于增强哺乳动物细胞的早期重编程效率并减少iPS细胞对癌症的威胁。这些发现表明植物激素在哺乳动物细胞可塑性生物学中的新作用。

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