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Small molecule compound induces chromatin de-condensation and facilitates induced pluripotent stem cell generation

文献类型：期刊论文

作者Wei, Xiaoyuan1,2; Chen, Yueting3; Xu, Yongyu1,2; Zhan, Yang3; Zhang, Ru1; Wang, Min2; Hua, Qiuhong1; Gu, Haifeng2; Nan, Fajun3; Xie, Xin1,2
刊名JOURNAL OF MOLECULAR CELL BIOLOGY
出版日期2014-10
卷号6期号:5页码:409-420
ISSN号1674-2788
关键词induced pluripotent stem cells reprogramming CYT296 small molecule compound chromatin de-condensation chromatin remodeling HP1 alpha
DOI10.1093/jmcb/mju024
文献子类Article
英文摘要The revolutionary induced pluripotent stem cell (iPSC) technology provides a new means for cell replacement therapies and drug screening. Small molecule compounds have been found extremely useful to improve the generation of iPSCs and understand the reprogramming mechanism. Here we report the identification of 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. The derived iPSCs are genuinely pluripotent and support the development of two 'All-iPSC' mice by tetraploid complementation. CYT296 profoundly impacts heterochromatin formation without affecting cell viability. MEFs treated with CYT296 exhibit de-condensed chromatin structure with markedly reduced loci containing heterochromatin protein 1 alpha (HP1 alpha) and H3K9me3, which is very similar to the chromatin configuration in embryonic stemcells (ESCs). Given that an open chromatin structure serves as a hallmark of pluripotency and has to be acquired to fulfill reprogramming, we propose that CYT296 might facilitate this process by disrupting condensed chromatin, thereby creating a more favorable environment for reprogramming. In agreement of this idea, shRNA targeting HP1 alpha also promotes the generation of iPSCs. Thus current findings not only provide a novel chemical for efficient iPSC induction, but also suggest a new approach to regulate somatic cell reprogramming by targeting chromatin de-condensation with small molecules.
WOS关键词DNA-METHYLATION ; HETEROCHROMATIN ; HISTONE ; DIFFERENTIATION ; TRANSCRIPTION ; MAINTENANCE ; INDUCTION ; PROTEINS ; REVEAL ; MOUSE
资助项目Chinese Academy of Sciences[XDA01040301] ; Ministry of Science and Technology of China[2009CB940900] ; Ministry of Science and Technology of China[2011DFB30010] ; Ministry of Science and Technology of China[2011CB965104] ; National Natural Science Foundation of China[91213303] ; National Natural Science Foundation of China[31371511] ; National Natural Science Foundation of China[30725049]
WOS研究方向Cell Biology
语种英语
CSCD记录号CSCD:5291591
出版者OXFORD UNIV PRESS
WOS记录号WOS:000344615900006
源URL[http://119.78.100.183/handle/2S10ELR8/276877]  
专题国家新药筛选中心
中科院受体结构与功能重点实验室
新药研究国家重点实验室
通讯作者Xie, Xin
作者单位1.Tongji Univ, Shanghai Key Lab Signaling & Dis Res, Sch Life Sci & Technol, Lab Receptor Based Biomed, Shanghai 200092, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Wei, Xiaoyuan,Chen, Yueting,Xu, Yongyu,et al. Small molecule compound induces chromatin de-condensation and facilitates induced pluripotent stem cell generation[J]. JOURNAL OF MOLECULAR CELL BIOLOGY,2014,6(5):409-420.
APA Wei, Xiaoyuan.,Chen, Yueting.,Xu, Yongyu.,Zhan, Yang.,Zhang, Ru.,...&Xie, Xin.(2014).Small molecule compound induces chromatin de-condensation and facilitates induced pluripotent stem cell generation.JOURNAL OF MOLECULAR CELL BIOLOGY,6(5),409-420.
MLA Wei, Xiaoyuan,et al."Small molecule compound induces chromatin de-condensation and facilitates induced pluripotent stem cell generation".JOURNAL OF MOLECULAR CELL BIOLOGY 6.5(2014):409-420.

入库方式： OAI收割

来源：上海药物研究所

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