論文 - 詳細
| RRC ID | 49491 |
|---|---|
| 著者 | Nishimura K, Aizawa S, Nugroho FL, Shiomitsu E, Tran YTH, Bui PL, Borisova E, Sakuragi Y, Takada H, Kurisaki A, Hayashi Y, Fukuda A, Nakanishi M, Hisatake K. |
| タイトル | A Role for KLF4 in Promoting the Metabolic Shift via TCL1 during Induced Pluripotent Stem Cell Generation. |
| ジャーナル | Stem Cell Reports |
| Abstract |
Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) is accompanied by morphological, functional, and metabolic alterations before acquisition of full pluripotency. Although the genome-wide effects of the reprogramming factors on gene expression are well documented, precise mechanisms by which gene expression changes evoke phenotypic responses remain to be determined. We used a Sendai virus-based system that permits reprogramming to progress in a strictly KLF4-dependent manner to screen for KLF4 target genes that are critical for the progression of reprogramming. The screening identified Tcl1 as a critical target gene that directs the metabolic shift from oxidative phosphorylation to glycolysis. KLF4-induced TCL1 employs a two-pronged mechanism, whereby TCL1 activates AKT to enhance glycolysis and counteracts PnPase to diminish oxidative phosphorylation. These regulatory mechanisms described here highlight a central role for a reprogramming factor in orchestrating the metabolic shift toward the acquisition of pluripotency during iPSC generation. |
| 巻・号 | 8(3) |
| ページ | 787-801 |
| 公開日 | 2017-3-14 |
| DOI | 10.1016/j.stemcr.2017.01.026 |
| PII | S2213-6711(17)30042-5 |
| PMID | 28262547 |
| PMC | PMC5355680 |
| MeSH | Animals Cellular Reprogramming* / genetics Energy Metabolism* Gene Expression Profiling Gene Expression Regulation Glycolysis Induced Pluripotent Stem Cells / cytology* Induced Pluripotent Stem Cells / metabolism* Kruppel-Like Factor 4 Kruppel-Like Transcription Factors / genetics Kruppel-Like Transcription Factors / metabolism* Mice Mitochondria / genetics Mitochondria / metabolism Oxidative Phosphorylation Protein Binding Proto-Oncogene Proteins / metabolism* Proto-Oncogene Proteins c-akt / metabolism Signal Transduction |
| IF | 6.032 |
| 引用数 | 10 |
| リソース情報 | |
| 遺伝子材料 | B6N Mouse BAC clone (RDB07573): B6Ng01-102P12. |
| ヒト・動物細胞 | Mouse iPSCs |