{"title":"A rapid chemical reprogramming system to generate human pluripotent stem cells","authors":"Yanglu Wang, Fangqi Peng, Zhihan Yang, Lin Cheng, Jingxiao Cao, Xiaodi Fu, Huanjing He, Ruyi Cai, Weizhen Zeng, Yingshuai Dong, Guanxian Chen, Gongxin Peng, Shijia Liuyang, Guan Wang, Jinlin Wang, Rong Mu, Cheng Li, Jingyang Guan, Hongkui Deng","doi":"10.1038/s41589-024-01799-8","DOIUrl":null,"url":null,"abstract":"<p>Chemical reprogramming enables the generation of human pluripotent stem (hCiPS) cells from somatic cells using small molecules, providing a promising strategy for regenerative medicine. However, the current method is time consuming, and some cell lines from different donors are resistant to chemical induction, limiting the utility of this approach. Here, we developed a fast reprogramming system capable of generating hCiPS cells in as few as 10 days. This accelerated method enables efficient generation of hCiPS cells with a consistent 100% success rate across 15 different donors, increasing efficiency by over 20-fold within 16 days, especially for previously resistant cells. Mechanistically, we identified KAT3A/KAT3B and KAT6A as key epigenetic obstacles; suppressing these factors facilitated the transition of somatic cells to a poised state by triggering switches in the epigenome. These results highlight the superiority of this system for generating hCiPS cells, which represents a next-generation approach for manufacturing cells for further applications.</p><figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"48 1","pages":""},"PeriodicalIF":12.9000,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature chemical biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s41589-024-01799-8","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Chemical reprogramming enables the generation of human pluripotent stem (hCiPS) cells from somatic cells using small molecules, providing a promising strategy for regenerative medicine. However, the current method is time consuming, and some cell lines from different donors are resistant to chemical induction, limiting the utility of this approach. Here, we developed a fast reprogramming system capable of generating hCiPS cells in as few as 10 days. This accelerated method enables efficient generation of hCiPS cells with a consistent 100% success rate across 15 different donors, increasing efficiency by over 20-fold within 16 days, especially for previously resistant cells. Mechanistically, we identified KAT3A/KAT3B and KAT6A as key epigenetic obstacles; suppressing these factors facilitated the transition of somatic cells to a poised state by triggering switches in the epigenome. These results highlight the superiority of this system for generating hCiPS cells, which represents a next-generation approach for manufacturing cells for further applications.
期刊介绍：
Nature Chemical Biology stands as an esteemed international monthly journal, offering a prominent platform for the chemical biology community to showcase top-tier original research and commentary. Operating at the crossroads of chemistry, biology, and related disciplines, chemical biology utilizes scientific ideas and approaches to comprehend and manipulate biological systems with molecular precision.
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