Stimulation of Somatic Cell Reprogramming by ERas-Akt-FoxO1 Signaling Axis
文献类型：期刊论文
| 作者 | Yu, Y; Liang, D; Tian, Q; Chen, XN; Jiang, B; Chou, BK; Hu, P; Cheng, LZ; Gao, P; Li, JS |
| 刊名 | STEM CELLS
 |
| 出版日期 | 2014 |
| 卷号 | 32期号:2页码:349-363 |
| 关键词 | ERas Akt FoxO1 Reprogramming Induced pluripotent stem cells |
| 通讯作者 | Wang, G (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,gwang@sibcb.ac.cn |
| 英文摘要 | Reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) shares much similarity to the cancer initiation process, and the molecular mechanisms underlying both processes remain to be elucidated. Here, we report that a tumor- or embryonic stem cell-specific Ras gene ERas, which encodes a constitutively active form of GTPase, and its downstream Phosphoinositide-3 kinase/Akt signaling pathway are important facilitators for the somatic reprogramming process. We found that overexpression of ERas retrovirally enhanced mouse iPSC induction while ERas knockdown repressed it. Modulation of Akt signaling by genetic or chemical means greatly impacted the reprogramming efficiency. Forced expression of a constitutively active Akt1 gene could rescue the reduced efficiency resulting from ERas knockdown, and point-mutation analyses further revealed that ERas is tightly coupled with Akt signaling to enhance reprogramming. Mechanistically, the forkhead transcription factor FoxO1 can function as a barrier to the iPSC induction, and the inactivation of FoxO1 by Akt-dependent phosphorylation largely accounts for the enhancing effect of ERas-Akt signaling on reprogramming. Collectively, these results unravel the significance of the ERas-Akt-FoxO1 signaling axis in iPSC generation, suggesting a possibly shared molecular basis for both somatic reprogramming and cancer initiation. Stem Cells2014;32:349-363 |
| 学科主题 | Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology |
| 类目[WOS] | Cell & Tissue Engineering ; Biotechnology & Applied Microbiology ; Oncology ; Cell Biology ; Hematology |
| 关键词[WOS] | PLURIPOTENT STEM-CELLS ; SMALL-MOLECULE COMPOUNDS ; EXPRESSED RAS ERAS ; IPS CELLS ; DEFINED FACTORS ; HIGH-EFFICIENCY ; ES CELLS ; C-MYC ; GENERATION ; MOUSE |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000330742100003 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/148]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Yu, Y,Liang, D,Tian, Q,et al. Stimulation of Somatic Cell Reprogramming by ERas-Akt-FoxO1 Signaling Axis[J]. STEM CELLS,2014,32(2):349-363. |
| APA | Yu, Y.,Liang, D.,Tian, Q.,Chen, XN.,Jiang, B.,...&Wang, G.(2014).Stimulation of Somatic Cell Reprogramming by ERas-Akt-FoxO1 Signaling Axis.STEM CELLS,32(2),349-363. |
| MLA | Yu, Y,et al."Stimulation of Somatic Cell Reprogramming by ERas-Akt-FoxO1 Signaling Axis".STEM CELLS 32.2(2014):349-363. |
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