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A kinase inhibitor screen identifies small-molecule enhancers of reprogramming and iPS cell generation

Author

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  • Zhonghan Li

    (Program for RNA Biology, Sanford-Burnham Medical Research Institute
    Chemical Biology Program, University of Massachusetts Medical School)

  • Tariq M. Rana

    (Program for RNA Biology, Sanford-Burnham Medical Research Institute
    Chemical Biology Program, University of Massachusetts Medical School
    University of California)

Abstract

Somatic cells can be reprogrammed to form embryonic stem cell-like induced pluripotent stem cells (iPSCs), but the process suffers from low efficiency and the underlying molecular mechanisms that control reprogramming remain poorly understood. Here we perform an inhibitor screen to identify kinases that enhance, or present a barrier to, reprogramming. In particular, inhibitors of p38, inositol trisphosphate 3-kinase, and Aurora A kinase potently enhance iPSC generation, and iPSCs derived from inhibitor-treated somatic cells are capable of reaching a fully reprogrammed state. Knockdown of target kinases by short interfering RNAs confirms that they function as barrier genes. We show that Aurora A kinase, which functions in centrosome activity and spindle assembly, is highly induced during reprogramming and inhibits Akt-mediated inactivation of GSK3β, resulting in compromised reprogramming efficiency. Together, our results not only identify new compounds that enhance iPSC generation but also shed new light on the function of Aurora A kinase in the reprogramming process.

Suggested Citation

  • Zhonghan Li & Tariq M. Rana, 2012. "A kinase inhibitor screen identifies small-molecule enhancers of reprogramming and iPS cell generation," Nature Communications, Nature, vol. 3(1), pages 1-11, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms2059
    DOI: 10.1038/ncomms2059
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    Cited by:

    1. Yangyang Yuan & Chenwei Wang & Xuran Zhuang & Shaofeng Lin & Miaomiao Luo & Wankun Deng & Jiaqi Zhou & Lihui Liu & Lina Mao & Wenbo Peng & Jian Chen & Qiangsong Wang & Yilai Shu & Yu Xue & Pengyu Huan, 2022. "PIM1 promotes hepatic conversion by suppressing reprogramming-induced ferroptosis and cell cycle arrest," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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