ArticleStem cells (Dayton, Ohio)2012
5-Aminoimidazole-4-carboxyamide ribonucleoside induces G(1)/S arrest and Nanog downregulation via p53 and enhances erythroid differentiation.
Article in Stem cells (Dayton, Ohio), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- AICAr, a Widely Used AMPK Activator with Important AMPK-Independent Effects: A Systematic Review.Cells · 2021Pooled it
- Mitochondrial dynamics imbalance in hepatocellular carcinoma: from molecular mechanisms to new strategies for targeted therapy.Translational cancer research · 2026Review
- Coupling of stemness maintenance with cell cycle control in stem cells.Frontiers in cell and developmental biology · 2025Review
- NANOG regulates epithelial-mesenchymal transition via AMPK/mTOR signalling pathway in ovarian cancer SKOV-3 and A2780 cells.Journal of cellular and molecular medicine · 2022Article
- Joint single-cell multiomic analysis in Wnt3a induced asymmetric stem cell division.Nature communications · 2021Article
- Article
- AICAR Stimulates the Pluripotency Transcriptional Complex in Embryonic Stem Cells Mediated by PI3K, GSK3β, and β-Catenin.ACS omega · 2020Article
- The ribonucleoside AICAr induces differentiation of myeloid leukemia by activating the ATR/Chk1 via pyrimidine depletion.The Journal of biological chemistry · 2019Article
- Why AMPK agonists not known to be stressors may surprisingly contribute to miscarriage or hinder IVF/ART.Journal of assisted reproduction and genetics · 2018Review
- Single-Cell Quantification of Protein Degradation Rates by Time-Lapse Fluorescence Microscopy in Adherent Cell Culture.Journal of visualized experiments : JoVE · 2018Article
- A Comparative Proteome Profile of Female Mouse Gonads Suggests a Tight Link between the Electron Transport Chain and Meiosis Initiation.Molecular & cellular proteomics : MCP · 2018Article
- CoQ10 increases mitochondrial mass and polarization, ATP and Oct4 potency levels, and bovine oocyte MII during IVM while decreasing AMPK activity and oocyte death.Journal of assisted reproduction and genetics · 2017Article
- Dormant Pluripotent Cells Emerge during Neural Differentiation of Embryonic Stem Cells in a FoxO3-Dependent Manner.Molecular and cellular biology · 2017Article
- Departure from optimal OThe Journal of reproduction and development · 2017Article
- Commonly used fertility drugs, a diet supplement, and stress force AMPK-dependent block of stemness and development in cultured mammalian embryos.Journal of assisted reproduction and genetics · 2016Article
- Metformin and AICAR regulate NANOG expression via the JNK pathway in HepG2 cells independently of AMPK.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- The role of NANOG transcriptional factor in the development of malignant phenotype of cancer cells.Cancer biology & therapy · 2016Review
- miR-134 Modulates the Proliferation of Human Cardiomyocyte Progenitor Cells by Targeting Meis2.International journal of molecular sciences · 2015Article
- Increased culture density is linked to decelerated proliferation, prolonged G1 phase, and enhanced propensity for differentiation of self-renewing human pluripotent stem cells.Stem cells and development · 2015Article
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Molecular mechanisms of how energy metabolism affects embryonic stem cell (ESC) pluripotency remain unclear. AMP-activated protein kinase (AMPK), a key regulator for controlling energy metabolism, is activated in response to ATP-exhausting stress. We investigated whether cellular energy homeostasis is associated with maintenance of self-renewal and pluripotency in mouse ESCs (mESCs) by using 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR) as an activator of AMPK. We demonstrate that AICAR treatment activates the p53/p21 pathway and markedly inhibits proliferation of R1 mESCs by inducing G(1) /S-phase cell cycle arrest, without influencing apoptosis. Treatment with AICAR also significantly reduces pluripotent stem cell markers, Nanog and stage-specific embryonic antigen-1, in the presence of leukemia inhibitory factor, without affecting expression of Oct4. H9 human ESCs also responded to AICAR with induction of p53 activation and repression of Nanog expression. AICAR reduced Nanog mRNA levels in mESCs transiently, an effect not due to expression of miR-134 which can suppress Nanog expression. AICAR induced Nanog degradation, an effect inhibited by MG132, a proteasome inhibitor. Although AICAR reduced embryoid body formation from mESCs, it increased expression levels of erythroid cell lineage markers (Ter119, GATA1, Klf1, Hbb-b, and Hbb-bh1). Although erythroid differentiation was enhanced by AICAR, endothelial lineage populations were remarkably reduced in AICAR-treated cells. Our results suggest that energy metabolism regulated by AMPK activity may control the balance of self-renewal and differentiation of ESCs.
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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.