論文 - 詳細
| RRC ID | 11845 |
|---|---|
| 著者 | Li Y, Zhang Q, Yin X, Yang W, Du Y, Hou P, Ge J, Liu C, Zhang W, Zhang X, Wu Y, Li H, Liu K, Wu C, Song Z, Zhao Y, Shi Y, Deng H. |
| タイトル | Generation of iPSCs from mouse fibroblasts with a single gene, Oct4, and small molecules. |
| ジャーナル | Cell Res |
| 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. |
| 巻・号 | 21(1) |
| ページ | 196-204 |
| 公開日 | 2011-1-1 |
| DOI | 10.1038/cr.2010.142 |
| PII | cr2010142 |
| PMID | 20956998 |
| PMC | PMC3193405 |
| MeSH | Animals Cellular Reprogramming / drug effects Fibroblasts / cytology* Gene Expression Profiling Induced Pluripotent Stem Cells / metabolism* Kruppel-Like Factor 4 Kruppel-Like Transcription Factors / genetics Kruppel-Like Transcription Factors / metabolism Mice Octamer Transcription Factor-3 / genetics Octamer Transcription Factor-3 / metabolism* Proto-Oncogene Proteins c-myc / genetics Proto-Oncogene Proteins c-myc / metabolism Pyridines / pharmacology Pyrimidines / pharmacology SOXB1 Transcription Factors / genetics SOXB1 Transcription Factors / metabolism |
| IF | 20.507 |
| 引用数 | 210 |
| WOS 分野 | CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 36 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC00771 |