MicroRNA modulation induced by AICA ribonucleotide in J1 mouse ES cells.
MicroRNA modulation induced by AICA ribonucleotide in J1 mouse ES cells.
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J1 小鼠 ES 细胞中 AICA 核糖核苷酸诱导的 MicroRNA 调节
DOI：
10.1371/journal.pone.0103724
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Shi X;YongyanWu;Ai Z;Du J;Cao L;Guo Z;Zhang Y
ES细胞可以无限繁殖、保持自我更新并分化为身体的几乎任何细胞类型。这些特性使它们在胚胎发育，再生医学和器官移植的研究中具有价值。MicroRNA（miRNAs）被认为在胚胎干细胞（ES细胞）的维持和分化中具有重要的功能。有研究表明，强的外界刺激，如短暂的低pH和缺氧应激，有利于诱导多能干细胞（iPS细胞）的形成。AICAR是一种AMP激活的蛋白激酶激活剂，能使细胞处于能量应激状态。我们在前期的研究中已经证实AICAR可以通过调节蛋白质表达来维持J1小鼠ES细胞的多能性，但其对ES细胞miRNA表达的影响尚不清楚。在这项研究中，我们进行了小RNA高通量测序研究AICAR对J1小鼠ES细胞的影响，通过比较AICAR处理的细胞和未处理的细胞的miRNA表达模式。结果表明AICAR可以显著调节多种miRNAs的表达，包括那些在ES细胞发育中起关键作用的miRNAs。筛选出差异表达的miRNAs，并通过实时荧光定量PCR进行验证。对于鉴定出的差异表达的miRNAs，进行了关于多能性和分化相关的miRNAs与其靶标的进一步研究。此外，miR-134在AICAR处理后显著下调，并且这被认为与上调的多能性标志物Nanog和Sox 2直接相关。最后，AICAR处理后Myc显著下调;因此，我们预测了可能靶向Myc的miRNA，并确定AICAR诱导的miR-34 a，34 b和34 c上调可以抑制J1小鼠ES细胞中Myc的表达。综上所述，我们的研究为AICAR在ES细胞多能性维持中提供了新的机制，并为AICAR在iPS细胞生成中的应用提供了新的见解。
ES cells can propagate indefinitely, maintain self-renewal, and differentiate into almost any cell type of the body. These properties make them valuable in the research of embryonic development, regenerative medicine, and organ transplantation. MicroRNAs (miRNAs) are considered to have essential functions in the maintenance and differentiation of embryonic stem cells (ES cells). It was reported that, strong external stimuli, such as a transient low-pH and hypoxia stress, were conducive to the formation of induced pluripotent stem cells (iPS cells). AICA ribonucleotide (AICAR) is an AMP-activated protein kinase activator, which can let cells in the state of energy stress. We have demonstrated that AICAR can maintain the pluripotency of J1 mouse ES cells through modulating protein expression in our previous research, but its effects on ES cell miRNA expression remain unknown. In this study, we conducted small RNA high-throughput sequencing to investigate AICAR influence on J1 mouse ES cells by comparing the miRNA expression patterns of the AICAR-treated cells and those without treatment. The result showed that AICAR can significantly modulate the expression of multiple miRNAs, including those have crucial functions in ES cell development. Some differentially expressed miRNAs were selected and confirmed by real-time PCR. For the differently expressed miRNAs identified, further study was conducted regarding the pluripotency and differentiation associated miRNAs with their targets. Moreover, miR-134 was significantly down-regulated after AICAR treatment, and this was suggested to be directly associated with the up-regulated pluripotency markers, Nanog and Sox2. Lastly, Myc was significantly down-regulated after AICAR treatment; therefore, we predicted miRNAs that may target Myc and identified that AICAR induced up-regulation of miR-34a, 34b, and 34c can repress Myc expression in J1 mouse ES cells. Taken together, our study provide a new mechanism for AICAR in ES cells pluripotency maintenance and give insight for its usage in iPS cells generation.
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影响因子：
11.2
作者：
Huang YW;Liu JC;Deatherage DE;Luo J;Mutch DG;Goodfellow PJ;Miller DS;Huang TH
通讯作者：
Huang TH
影响因子：
7.2
作者：
Merrill, Bradley J.
通讯作者：
Merrill, Bradley J.
影响因子：
16.8
作者：
Kim, Myoung Ok;Kim, Sung-Hyun;Dong, Zigang
通讯作者：
Dong, Zigang
DOI：
10.1073/pnas.0608156103
发表时间：
2006-11-14
影响因子：
11.1
作者：
Chen, Shuibing;Do, Jeong Tae;Ding, Sheng
通讯作者：
Ding, Sheng
DOI：
10.1084/jem.20101438
发表时间：
2010-10-25
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Christophersen NS;Helin K
通讯作者：
Helin K