Folic Acid Supports Pluripotency and Reprogramming by Regulating LIF/STAT3 and MAPK/ERK Signaling.

Folic Acid Supports Pluripotency and Reprogramming by Regulating LIF/STAT3 and MAPK/ERK Signaling.
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叶酸通过调节 LIF/STAT3 和 MAPK/ERK 信号转导支持多能性和重编程。

DOI:
10.1089/scd.2016.0091
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发表时间:
2017
期刊:
Stem Cells Dev
影响因子:
--
通讯作者:
Kang, Jiuhong
Kang, Jiuhong
中科院分区:
其他
文献类型:
--
作者:
Wang, Zikang;Wang, Kai;Duan, Tao;Kang, Jiuhong

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多能干细胞具有自我更新和分化的特性,是疾病治疗的理想细胞来源。多能干细胞是异质性的,由幼稚干细胞以及致敏的上胚层干细胞组成。然而,维持幼稚多能干细胞的策略和机制仍不清楚。在这项研究中,我们发现,叶酸(FA)维持小鼠胚胎干细胞(ESC)的多能性,并使长期维持幼稚状态的胚胎干细胞在CHIR 99021条件下。机制实验表明,FA作用后,STAT 3与importin α5的相互作用增强,STAT 3通路部分介导了FA的作用。同时,MEK/ERK信号也在FA下游发挥作用,维持ESC的多能性。此外,FA显着促进小鼠体细胞重编程。总的来说,我们的研究确定了维持同质ESC的有效化学条件,并强调了LIF/STAT 3和MEK/ERK信号传导在幼稚ESC多能性中的重要作用。
Pluripotent stem cells act as an excellent cell source for disease therapy because of its specific characteristics of self-renewal and differentiation. Pluripotent stem cells are heterogeneous, consisting of naive stem cells as well as primed epiblast stem cells. However, the strategies and mechanisms of maintaining naive pluripotent stem cells remain unclear. In this study, we found that folic acid (FA) sustained mouse embryonic stem cell (ESC) pluripotency and enabled long-term maintenance of the naive state of ESCs under CHIR99021 conditions. Mechanistic experiments showed that STAT3 pathway partially mediated the effect of FA after which the interaction between STAT3 and importin α5 was enhanced. Meanwhile, MEK/ERK signaling also acted downstream of FA in maintaining ESC pluripotency. Furthermore, FA significantly promoted mouse somatic cell reprogramming. Overall, our study identified an effective chemical condition for maintaining homogeneous ESCs and highlighted the important roles of LIF/STAT3 and MEK/ERK signaling in naive ESC pluripotency.
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