ArticleNucleic acids research2012
Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3 signaling and results in loss of embryonic stem cell identity.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- What do DNA methylation studies tell us about depression? A systematic review.Translational psychiatry · 2019Pooled it
- Cell identity and 5-hydroxymethylcytosine.Epigenetics & chromatin · 2025Review
- Epigenetic Therapies in Melanoma-Targeting DNA Methylation and Histone Modification.Biomedicines · 2025Review
- 5-Hydroxymethylcytosine: Far Beyond the Intermediate of DNA Demethylation.International journal of molecular sciences · 2024Review
- An Overview of Global, Local, and Base-Resolution Methods for the Detection of 5-Hydroxymethylcytosine in Genomic DNA.Methods in molecular biology (Clifton, N.J.) · 2024Review
- TET (Ten-eleven translocation) family proteins: structure, biological functions and applications.Signal transduction and targeted therapy · 2023Review
- Induced hepatic stem cells maintain self-renewal through the high expression of Myc coregulated by TET1 and CTCF.Cell & bioscience · 2022Article
- Epigenetic Mechanisms of Epidermal Differentiation.International journal of molecular sciences · 2022Review
- A Non-redundant Function of MNS5: A Class I α-1, 2 Mannosidase, in the Regulation of Endoplasmic Reticulum-Associated Degradation of Misfolded Glycoproteins.Frontiers in plant science · 2022Article
- Article
- Role of TET1 and 5hmC in an Obesity-Linked Pathway Driving Cancer Stem Cells in Triple-Negative Breast Cancer.Molecular cancer research : MCR · 2020Article
- TET family regulates the embryonic pluripotency of porcine preimplantation embryos by maintaining the DNA methylation level ofEpigenetics · 2020Article
- TET1 Directs Chondrogenic Differentiation by Regulating SOX9 Dependent Activation ofJBMR plus · 2020Article
- Fasciola gigantica excretory-secretory products (FgESPs) modulate the differentiation and immune functions of buffalo dendritic cells through a mechanism involving DNMT1 and TET1.Parasites & vectors · 2020Article
- TET1 Deficiency Impairs Morphogen-free Differentiation of Human Embryonic Stem Cells to Neuroectoderm.Scientific reports · 2020Article
- Nono deficiency compromises TET1 chromatin association and impedes neuronal differentiation of mouse embryonic stem cells.Nucleic acids research · 2020Article
- Dysregulation of Neuronal Genes by Fetal-Neonatal Iron Deficiency Anemia Is Associated with Altered DNA Methylation in the Rat Hippocampus.Nutrients · 2019Article
- Oxygen gradients can determine epigenetic asymmetry and cellular differentiation via differential regulation of Tet activity in embryonic stem cells.Nucleic acids research · 2018Article
- STAT3-Inducible Mouse ESCs: A Model to Study the Role of STAT3 in ESC Maintenance and Lineage Differentiation.Stem cells international · 2018Article
- Leukemia Inhibitory Factor Promotes Aggressiveness of Chordoma.Oncology research · 2017Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The TET family of FE(II) and 2-oxoglutarate-dependent enzymes (Tet1/2/3) promote DNA demethylation by converting 5-methylcytosine to 5-hydroxymethylcytosine (5hmC), which they further oxidize into 5-formylcytosine and 5-carboxylcytosine. Tet1 is robustly expressed in mouse embryonic stem cells (mESCs) and has been implicated in mESC maintenance. Here we demonstrate that, unlike genetic deletion, RNAi-mediated depletion of Tet1 in mESCs led to a significant reduction in 5hmC and loss of mESC identity. The differentiation phenotype due to Tet1 depletion positively correlated with the extent of 5hmC loss. Meta-analyses of genomic data sets suggested interaction between Tet1 and leukemia inhibitory factor (LIF) signaling. LIF signaling is known to promote self-renewal and pluripotency in mESCs partly by opposing MAPK/ERK-mediated differentiation. Withdrawal of LIF leads to differentiation of mESCs. We discovered that Tet1 depletion impaired LIF-dependent Stat3-mediated gene activation by affecting Stat3's ability to bind to its target sites on chromatin. Nanog overexpression or inhibition of MAPK/ERK signaling, both known to maintain mESCs in the absence of LIF, rescued Tet1 depletion, further supporting the dependence of LIF/Stat3 signaling on Tet1. These data support the conclusion that analysis of mESCs in the hours/days immediately following efficient Tet1 depletion reveals Tet1's normal physiological role in maintaining the pluripotent state that may be subject to homeostatic compensation in genetic models.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.