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Inhibition of methyl-CpG binding domain protein 3 (MBD3) for deterministic and synchronized reprogramming to pluripotency

In vitro studies suggest depletion of Mbd3 can improve the efficiency of reprogramming somatic cells to a pluripotent state over short time periods. Expression of Oct4, Sox2, Klf4 and c-Myc (Myc) reprograms somatic cells into induced pluripotent stem (iPS) cells. In murine epiblast stem cells, small interfering RNA against Mbd3 improved the reprogramming efficiency of the 4 transcription factors to 80% at 5 days, whereas control siRNA caused a 10% improvement. In Mbd3-depleted mouse embryonic fibroblasts and human fibroblasts, expression of the transcription factors resulted in about 100% reprogramming efficiency by day 8, whereas wild-type cells had only 20% efficiency. Next steps could include incorporating MBD3 depletion into reprogramming protocols that companies use to generate isogenic and disease-relevant iPS cell lines.

SciBX 6(40); doi:10.1038/scibx.2013.1144
Published online Oct. 17, 2013

Patent pending; available for nonexclusive licensing

Rais, Y. et al. Nature; published online Sept. 18, 2013;
Contact: Jacob H. Hanna, Weizmann Institute of Science, Rehovot, Israel