ArticleNature cell biology2015
Autophagy and mTORC1 regulate the stochastic phase of somatic cell reprogramming.
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Article in Nature cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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61citing papers in PubMed
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Who cites it
61 citing papers in PubMed.
- Chemically Derived Hepatic Progenitors Are Reprogrammed through Autophagy Suppression by A83-01.International journal of stem cells · 2026Article
- Hyperactivation of mTORC1 blocks stem cell fate transitions through TFE3-NuRD association.EMBO reports · 2026Article
- Biomimetic ECM collagen hydrogel induces chondrogenic differentiation of BMSCs by activating autophagy through POU5F1-mediated AMPK/mTOR signaling pathway.Theranostics · 2026Article
- Article
- The Role of Autophagy in Long-term Effects of Spinal Cord Injury: Does Exosome Change the Autophagy Process and Vice Versa?Advanced pharmaceutical bulletin · 2025Review
- Perinuclear mitochondrial clustering for mesenchymal-to-epithelial transition in pluripotency induction.Stem cell reports · 2025Article
- The Role of Autophagy in the Regulation of Bidirectional Relationships in Diabetic Periodontitis.Journal of inflammation research · 2025Review
- Krüppel-like factors in mitochondrial quality control.Frontiers in physiology · 2025Review
- Review
- A fast chemical reprogramming system promotes cell identity transition through a diapause-like state.Nature cell biology · 2023Article
- Mitochondrial regulation in human pluripotent stem cells during reprogramming and β cell differentiation.Frontiers in endocrinology · 2023Review
- Metabolic control of induced pluripotency.Frontiers in cell and developmental biology · 2023Review
- Autophagy and pluripotency: self-eating your way to eternal youth.Trends in cell biology · 2022Review
- BNIP3 (BCL2 interacting protein 3) regulates pluripotency by modulating mitochondrial homeostasis via mitophagy.Cell death & disease · 2022Article
- mRNA Translation Is Dynamically Regulated to Instruct Stem Cell Fate.Frontiers in molecular biosciences · 2022Review
- Forkhead box family transcription factors as versatile regulators for cellular reprogramming to pluripotency.Cell regeneration (London, England) · 2021Article
- Regulation and metabolic functions of mTORC1 and mTORC2.Physiological reviews · 2021Review
- Inhibition of Syk promotes chemical reprogramming of fibroblasts via metabolic rewiring and HThe EMBO journal · 2021Article
- PINK1-mediated mitophagy maintains pluripotency through optineurin.Cell proliferation · 2021Article
- Reprogramming progressive cells display low CAG promoter activity.Stem cells (Dayton, Ohio) · 2021Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors.
Yasong WuKey Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Yuan Li1] Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China [2] School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
Hui ZhangKey Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Yinghua HuangKey Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Ping ZhaoKey Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Yujia TangKey Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Xiaohui QiuKey Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Yue YingKey Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Wen Li1] Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China [2] Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Su NiKey Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Meng Zhang1] Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China [2] School of Life Sciences, Anhui University, Hefei 230601, China.
Longqi LiuKey Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Yan XuKey Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Qiang ZhuangKey Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Zhiwei LuoKey Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Christina BendaKey Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Hong SongKey Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Baohua LiuHealth Science Center, Shenzhen University, Shenzhen 518060, China.
Liangxue LaiKey Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Xingguo LiuKey Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Hung-Fat Tse1] Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China [2] Shenzhen Institutes of Research and Innovation, the University of Hong Kong, Hong Kong SAR, China [3] Hong Kong-Guangdong Joint Laboratory on Stem Cell and Regenerative Medicine, the University of Hong Kong and Guangzhou Institutes of Biomedicine and Health, China.
Xichen BaoKey Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Wai-Yee ChanCUHK-GIBH Joint Research Laboratory of Stem Cells and Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong, China.
Miguel A Esteban1] Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China [2] Hong Kong-Guangdong Joint Laboratory on Stem Cell and Regenerative Medicine, the University of Hong Kong and Guangzhou Institutes of Biomedicine and Health, China.
Baoming Qin1] Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China [2] Hong Kong-Guangdong Joint Laboratory on Stem Cell and Regenerative Medicine, the University of Hong Kong and Guangzhou Institutes of Biomedicine and Health, China.
Duanqing Pei1] Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China [2] Hong Kong-Guangdong Joint Laboratory on Stem Cell and Regenerative Medicine, the University of Hong Kong and Guangzhou Institutes of Biomedicine and Health, China.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We describe robust induction of autophagy during the reprogramming of mouse fibroblasts to induced pluripotent stem cells by four reprogramming factors (Sox2, Oct4, Klf4 and c-Myc), henceforth 4F. This process occurs independently of p53 activation, and is mediated by the synergistic downregulation of mechanistic target of rapamycin complex 1 (mTORC1) and the induction of autophagy-related genes. The 4F coordinately repress mTORC1, but bifurcate in their regulation of autophagy-related genes, with Klf4 and c-Myc inducing them but Sox2 and Oct4 inhibiting them. On one hand, inhibition of mTORC1 facilitates reprogramming by promoting cell reshaping (mitochondrial remodelling and cell size reduction). On the other hand, mTORC1 paradoxically impairs reprogramming by triggering autophagy. Autophagy does not participate in cell reshaping in reprogramming but instead degrades p62, whose accumulation in autophagy-deficient cells facilitates reprogramming. Our results thus reveal a complex signalling network involving mTORC1 inhibition and autophagy induction in the early phase of reprogramming, whose delicate balance ultimately determines reprogramming efficiency.
Indexed as
AnimalsApoptosis Regulatory ProteinsAutophagyAutophagy-Related Protein 5Beclin-1Cells, CulturedCellular ReprogrammingClass III Phosphatidylinositol 3-KinasesDown-RegulationFibroblastsInduced Pluripotent Stem CellsKruppel-Like Factor 4Kruppel-Like Transcription FactorsMechanistic Target of Rapamycin Complex 1MiceMice, KnockoutApoptosis Regulatory ProteinsAtg5 protein, mouseAutophagy-Related Protein 5Beclin-1Becn1 protein, mouseClass III Phosphatidylinositol 3-KinasesKlf4 protein, mouseKruppel-Like Factor 4Kruppel-Like Transcription FactorsMechanistic Target of Rapamycin Complex 1Microtubule-Associated ProteinsMultiprotein ComplexesMyc protein, mouseOctamer Transcription Factor-3Pou5f1 protein, mouseProto-Oncogene Proteins c-mycRNA, Small InterferingSox2 protein, mouseSOXB1 Transcription FactorsTOR Serine-Threonine KinasesTumor Suppressor Protein p53
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