Title | Generation of iPSCs from mouse fibroblasts with a single gene, Oct4, and small molecules |
Authors | Li, Yanqin Zhang, Qiang Yin, Xiaolei Yang, Weifeng Du, Yuanyuan Hou, Pingping Ge, Jian Liu, Chun Zhang, Weiqi Zhang, Xu Wu, Yetao Li, Honggang Liu, Kang Wu, Chen Song, Zhihua Zhao, Yang Shi, Yan Deng, Hongkui |
Affiliation | Peking Univ, Coll Life Sci, Dept Cell Biol & Genet, Beijing 100871, Peoples R China. Peking Univ, Shenzhen Grad Sch, Sch Chem Biol & Biotechnol, Lab Chem Genom, Shenzhen 518055, Peoples R China. Beijing Rui Pu Chen Chuang Biotech Inc, Beijing, Peoples R China. |
Keywords | pluripotentcy iPS cells oct4 reprogramming PLURIPOTENT STEM-CELLS DEFINED FACTORS INDUCTION EFFICIENCY SYSTEM SOX2 |
Issue Date | 2011 |
Publisher | 细胞研究英文版 |
Citation | CELL RESEARCH.2011,21,(1),196-204. |
Abstract | The introduction of four transcription factors Oct4, Klf4, Sox2 and c-Myc by viral transduction can induce reprogramming of somatic cells into induced pluripotent stem cells (iPSCs), but the use of iPSCs is hindered by the use of viral delivery systems. Chemical-induced reprogramming offers a novel approach to generating iPSCs without any viral vector-based genetic modification. Previous reports showed that several small molecules could replace some of the reprogramming factors although at least two transcription factors, Oct4 and Klf4, are still required to generate iPSCs from mouse embryonic fibroblasts. Here, we identify a specific chemical combination, which is sufficient to permit reprogramming from mouse embryonic and adult fibroblasts in the presence of a single transcription factor, Oct4, within 20 days, replacing Sox2, Klf4 and c-Myc. The iPSCs generated using this treatment resembled mouse embryonic stem cells in terms of global gene expression profile, epigenetic status and pluripotency both in vitro and in vivo. We also found that 8 days of Oct4 induction was sufficient to enable Oct4-induced reprogramming in the presence of the small molecules, which suggests that reprogramming was initiated within the first 8 days and was independent of continuous exogenous Oct4 expression. These discoveries will aid in the future generation of iPSCs without genetic modification, as well as elucidating the molecular mechanisms that underlie the reprogramming process. |
URI | http://hdl.handle.net/20.500.11897/162548 |
ISSN | 1001-0602 |
DOI | 10.1038/cr.2010.142 |
Indexed | SCI(E) PubMed 中国科技核心期刊(ISTIC) 中国科学引文数据库(CSCD) |
Appears in Collections: | 生命科学学院 化学生物学与生物技术学院 |