ArticleCell death & disease2016
Leukemia inhibitory factor (LIF) withdrawal activates mTOR signaling pathway in mouse embryonic stem cells through the MEK/ERK/TSC2 pathway.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 52 citations in OpenAlex.
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- Spatial dynamics of mTOR pathway activity during bovine embryo development.Frontiers in cell and developmental biology · 2026Article
- Regulation of TSC2 lysosome translocation and mitochondrial turnover by TSC2 acetylation status.Scientific reports · 2024Article
- Dynamic nucleolar phase separation influenced by non-canonical function of LIN28A instructs pluripotent stem cell fate decisions.Nature communications · 2024Article
- mTOR Plays an Important Role in the Stemness of Human Fetal Cartilage Progenitor Cells (hFCPCs).Tissue engineering and regenerative medicine · 2024Article
- Signalling pathway crosstalk stimulated by L-proline drives mouse embryonic stem cells to primitive-ectoderm-like cells.Development (Cambridge, England) · 2023Article
- An O-GlcNAc transferase pathogenic variant linked to intellectual disability affects pluripotent stem cell self-renewal.Disease models & mechanisms · 2023Article
- Increased expression of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase-3 is required for growth of mouse embryonic stem cells that are undergoing differentiation.Cytotechnology · 2023Article
- PDGFD switches on stem cell endothelial commitment.Angiogenesis · 2022Article
- Distinct transcription kinetics of pluripotent cell states.Molecular systems biology · 2022Article
- Leukemia inhibitory factor regulates Schwann cell proliferation and migration and affects peripheral nerve regeneration.Cell death & disease · 2021Article
- Recent technological advancements in stem cell research for targeted therapeutics.Drug delivery and translational research · 2020Review
- The novel application of cordycepin in maintaining stem cell pluripotency and increasing iPS cell generation efficiency.Scientific reports · 2020Article
- Autophagy and its role in regeneration and remodeling within invertebrate.Cell & bioscience · 2020Review
- FGF Signaling Pathway: A Key Regulator of Stem Cell Pluripotency.Frontiers in cell and developmental biology · 2020Review
- Changes in the Expression of Mitochondrial Morphology-Related Genes during the Differentiation of Murine Embryonic Stem Cells.Stem cells international · 2020Article
- Effects of leukemia inhibitory factor receptor on the adipogenic differentiation of human bone marrow mesenchymal stem cells.Molecular medicine reports · 2019Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leukemia inhibitory factor (LIF) is indispensable to maintain the pluripotent state of mouse embryonic stem cells (ESCs), but the mechanisms underlying the role of LIF/STAT3 pathway are yet poorly understood. Here we first showed that the LIF/STAT3-regulated signaling pathway contributes to the maintenance of self-renewal and pluripotency of mouse ESCs by suppressing mTOR (mammalian target of rapamycin), which is necessary for early differentiation. When LIF is withdrawn from culture medium, the mTOR activity rapidly increases as detected by phosphorylation of its targets - ribosomal protein S6 and translation factor 4EBP1. In turn, suppression of STAT3 phosphorylation on Tyr-705 by a specific small molecule WP1066 also activates phosphorylation of the mTOR target S6 ribosomal protein. LIF removal strongly activates ERK activity indicating that ERK can be involved in either direct phosphorylation of mTOR or phosphorylation of an upstream negative regulator of mTOR - TSC1/TSC2 proteins. According to western blotting data, LIF withdrawal leads to phosphorylation of TSC2 protein thereby relieving its negative effect on mTOR activity. mTOR activation is accompanied by a decrease of pluripotent gene expression Oct-4, Nanog, Sox2 and by an augmentation of fgf5 gene expression - a marker of post-implantation epiblast. Together, these data indicate that LIF-depleted mouse ESCs undergo a transition from the LIF/STAT3-supported pluripotent state to the FGFR/ERK-committed primed-like state with expression of early differentiation markers mediated through activation of mTOR signaling.
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