Activation of the imprinted Dlk1-Dio3 region correlates with pluripotency levels of mouse stem cells.
Activation of the imprinted Dlk1-Dio3 region correlates with pluripotency levels of mouse stem cells.
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印记 Dlk1-Dio3 区域的激活与小鼠干细胞的多能性水平相关
DOI：
10.1074/jbc.m110.131995
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发表时间：
2010-06-18
期刊：
影响因子：
--
通讯作者：
Zhou Q
中科院分区：
文献类型：
--
作者：
Liu L;Luo GZ;Yang W;Zhao X;Zheng Q;Lv Z;Li W;Wu HJ;Wang L;Wang XJ;Zhou Q
重编程效率低和多能性降低一直是诱导多能干细胞研究的两大障碍。一种有效、快速的早期评估iPS细胞多能性水平的方法将显著提高iPS细胞生成的成功率，促进其应用。我们在小鼠基因组中发现了一个保守的印迹区域，即Dlk1-Dio3区域，该区域在完全多能小鼠干细胞中被激活，但在部分多能小鼠干细胞中被抑制。该区域的激活程度与干细胞的多能性水平呈正相关。由该区域编码的哺乳动物保守的microrna簇在完全和部分多能干细胞中表现出显著的表达差异。来自该簇的一些microrna可能靶向多梳抑制复合体2 （PRC2）的组分，并可能形成一个反馈调节回路，导致该区域编码的所有基因和非编码rna在全多能干细胞中的表达。没有发现其他基因组区域在不同多能性水平的细胞系之间表现出如此明显的表达变化；因此，Dlk1-Dio3区域可以作为从部分多能性细胞中识别完全多能性iPS或胚胎干细胞的标记。这些发现也为理解iPS细胞重编程过程中的操作机制提供了一步，并有可能促进iPS细胞在再生医学和癌症治疗中的应用。
Low reprogramming efficiency and reduced pluripotency have been the two major obstacles in induced pluripotent stem (iPS) cell research. An effective and quick method to assess the pluripotency levels of iPS cells at early stages would significantly increase the success rate of iPS cell generation and promote its applications. We have identified a conserved imprinted region of the mouse genome, the Dlk1-Dio3 region, which was activated in fully pluripotent mouse stem cells but repressed in partially pluripotent cells. The degree of activation of this region was positively correlated with the pluripotency levels of stem cells. A mammalian conserved cluster of microRNAs encoded by this region exhibited significant expression differences between full and partial pluripotent stem cells. Several microRNAs from this cluster potentially target components of the polycomb repressive complex 2 (PRC2) and may form a feedback regulatory loop resulting in the expression of all genes and non-coding RNAs encoded by this region in full pluripotent stem cells. No other genomic regions were found to exhibit such clear expression changes between cell lines with different pluripotency levels; therefore, the Dlk1-Dio3 region may serve as a marker to identify fully pluripotent iPS or embryonic stem cells from partial pluripotent cells. These findings also provide a step forward toward understanding the operating mechanisms during reprogramming to produce iPS cells and can potentially promote the application of iPS cells in regenerative medicine and cancer therapy.