An Elaborate Regulation of Mammalian Target of Rapamycin Activity Is Required for Somatic Cell Reprogramming Induced by Defined Transcription Factors
| العنوان: | An Elaborate Regulation of Mammalian Target of Rapamycin Activity Is Required for Somatic Cell Reprogramming Induced by Defined Transcription Factors |
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| المؤلفون: | Wenqiang Liu, Haitao Wang, Jing He, Jiqin Zhang, Lan Kang, Zhaohui Kou, Tong Wu, Shaorong Gao, Bo Huang, Hongbing Zhang, Yu Zhang, Haibo Gao |
| المصدر: | Stem Cells and Development. 21:2630-2641 |
| بيانات النشر: | Mary Ann Liebert Inc, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Male, Mice, 129 Strain, Somatic cell, Induced Pluripotent Stem Cells, Biology, Gene Expression Regulation, Enzymologic, Mice, Tuberous Sclerosis Complex 2 Protein, Animals, RNA, Small Interfering, Transcription factor, PI3K/AKT/mTOR pathway, Cell Proliferation, Sirolimus, Gene knockdown, Cell growth, SOXB1 Transcription Factors, TOR Serine-Threonine Kinases, Tumor Suppressor Proteins, RPTOR, Cell Differentiation, Cell Biology, Hematology, Fibroblasts, Embryo, Mammalian, Specific Pathogen-Free Organisms, Cell biology, Enzyme Activation, Female, Signal transduction, Octamer Transcription Factor-3, Reprogramming, Signal Transduction, Developmental Biology |
| الوصف: | The mammalian target of the rapamycin (mTOR) signaling pathway functions in many cellular processes, including cell growth, proliferation, differentiation, and survival. Recent advances have demonstrated that differentiated somatic cells can be directly reprogrammed into the pluripotent state by overexpression of several pluripotency transcription factors. However, whether the mTOR signaling pathway is involved in this somatic cell-reprogramming process remains unknown. Here, we provide evidence that an elaborate regulation of the mTOR activity is required for the successful reprogramming of somatic cells to pluripotency. The reprogramming of somatic cells collected from the Tsc2(-/-) embryo, in which the mTOR activity is hyperactivated, is entirely inhibited. By taking advantage of the secondary inducible pluripotent stem (iPS) system, we demonstrate that either elevating the mTOR activity by Tsc2 shRNA knockdown or using high concentrations of rapamycin to completely block the mTOR activity in cells derived from iPS mice greatly impairs somatic cell reprogramming. Secondary iPS induction efficiency can only be elevated by elaborately regulating the mTOR activity. Taken together, our data demonstrate that the precise regulation of the mTOR activity plays a critical role in the successful reprogramming of somatic cells to form iPS cells. |
| تدمد: | 1557-8534 1547-3287 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::568739799a9cfc910af4046f99f85077Test https://doi.org/10.1089/scd.2012.0015Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....568739799a9cfc910af4046f99f85077 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15578534 15473287 |
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