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Logo of jbcThe Journal of Biological Chemistry
 
J Biol Chem. 2010 June 18; 285(25): e99949.
PMCID: PMC2885248

Unlocking Maximum iPS Potential♦

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

♦ See referenced article, J. Biol. Chem. 2010, 285, 19483–19490

The successful reprogramming of differentiated adult cells into induced pluripotent stem (iPS) 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 has somewhat limited their potential. A quick and effective method to determine which newly reprogrammed iPS cells have the highest pluripotency capacity would significantly increase the success rate of creating robust iPS cell lines and that issue has been examined in this Paper of the Week. Lei Liu and colleagues 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 level. What's more, the nearly 50 microRNAs (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 polycomb silencing complex 2 (PRC2), thus forming a feedback loop resulting in the expression of all proteins and RNAs encoded within the Dlk1-Dio3 region in pluripotent stem cells. This exciting study suggests that Dlk1-Dio3 activity may serve as a biomarker to identify fully pluripotent iPS cells, which not only provides more understanding about cellular reprogramming but also can advance the application of iPS cells in therapeutics.

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A working model for miRNA regulation of iPS pluripotency. In partially pluripotent cells, the Dlk1-Dio3 region is methylated by PRC2, and miRNA expression is repressed; in fully pluripotent cells, the Dlk1-Dio3 region is activated resulting in miRNA expression and inhibition of Dlk1-Dio3 methylation, producing a feedback loop to further increase mRNA and miRNA expression.

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Articles from The Journal of Biological Chemistry are provided here courtesy of American Society for Biochemistry and Molecular Biology