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SIMM discovers small molecules that induce chromatin de-condensation and facilitates iPSC generation
Update time: 2014-09-17
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The induced pluripotent stem cells (iPSC) has attracted enormous interests due toits potential biomedical applications. However, iPSC applicationsare hindered by safety concerns due to the use of oncogenes and incorporation of viralDNA sequences. And the mechanisms underlying reprogramming remain elusive. Many efforts have been taken to make iPSCs more amenable for therapeutic application.  

Recently, researchers from SIMM identified a novel chemical, CYT296, which improves OSKM-mediated induction of iPSCs for >10 folds and enables efficient reprogramming with only Oct4 in combination with other small molecules. Mechanism study indicated that CYT296 profoundly impacts heterochromatin formation. MEFs treated with CYT296 exhibit de-condensed chromatin structure with markedly reduced loci containing heterochromatin protein 1α (HP1α) and H3K9me3, which is very similar to the chromatin configuration in embryonic stem cells (ESCs). Given that an open chromatin structure serves as a hallmark of pluripotency and has to be acquired to fulfill reprogramming, it was propose that CYT296 might facilitate this process by disrupting condensed chromatin, thereby creating a more favorable environment for reprogramming. These findings were published in the Journal of Molecular Cell Biology.  

This work was supervised by Prof. XIE Xin  and Prof.  NAN Fajun. The first authors are Dr.  WEI Xiaoyuan(biology part) and Dr.CHEN Yueting  (chemistry part). This work was supported by grants from Chinese Academy of Sciences, Ministry of Science and Technology of China, and Shanghai Commissionof Science and Technology. 

Link to the articlehttp://jmcb.oxfordjournals.org/content/early/2014/06/16/jmcb.mju024.full.pdf+html 

 
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