June 2010

[JBC] Unlocking Maximum iPS Potential

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A working model for miRNA regulation of iPS pluripotency.

The successful reprogramming of differentiated adult cells into induced pluripotent stem cells has opened up a valuable new road for stem cell research. However, iPS cells do suffer from low reprogramming efficiency and reduced pluripotency, which somewhat has limited their potential. A quick and effective method to determine which newly reprogrammed iPS cells have the best pluripotency potential would significantly increase the success rate of creating robust iPS cell lines. In this study, the authors found that the conserved imprinted region Dlk1-Dio3 was activated in fully pluripotent mouse stem cells but repressed in partially pluripotent stem cells and that the degree of Dlk1-Dio3 activation positively correlated with pluripotency levels. What’s more, the miRNAs encoded by this region also exhibited significant expression differences between fully and partially pluripotent stem cells. Several of these miRNAs may target and repress the PRC2 gene-silencing complex, thus forming a feedback loop resulting in the expression of all proteins and RNAs encoded within the Dlk1-Dio3 region. This exciting study suggests that Dlk1-Dio3 activity may serve as a biomarker to identify fully pluripotent iPS cells. This not only provides more understanding about cellular reprogramming but also can advance the application of iPS cells in therapeutics.

Activation of the Imprinted Dlk1-Dio3 Region Correlates with Pluripotency Levels of Mouse Stem Cells

Lei Liu, Guan-Zheng Luo, Wei Yang, Xiaoyang Zhao, Qinyuan Zheng, Zhuo Lv, Wei Li, Hua-Jun Wu, Liu Wang, Xiu-Jie Wang and Qi Zhou

J. Biol. Chem., published online April 9, 2010

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