ArticleStem cells (Dayton, Ohio)2014
Nrf2, a regulator of the proteasome, controls self-renewal and pluripotency in human embryonic stem cells.
Article in Stem cells (Dayton, Ohio), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
108 citing papers in PubMed, 202 citations in OpenAlex.
- Proteostasis of organelles in aging and disease.The FEBS journal · 2026Review
- NRF2 deficiency impairs proliferation and survival of chicken primordial germ cells via oxidative stress, mitochondrial dysfunction and apoptosis.Poultry science · 2026Article
- The nuclear cap-binding complex safeguards stress-resistant protein synthesis and proliferation of stem cells.Science advances · 2026Article
- Dual targeting of the UPS and autophagy as a novel therapy for neurodegenerative proteinopathies.Frontiers in cellular neuroscience · 2026Review
- Volvariella volvacea polysaccharides alleviate acute liver injury by modulating Nrf2/NF-κB pathway in a dual manner.NPJ science of food · 2025Article
- Atrazine Induces Reproductive Toxicity in anBiomedicines · 2025Article
- Fosl2 facilitates chromatin accessibility to determine developmental events during follicular maturation.Nature communications · 2025Article
- An Update on Role of Ionizing Radiation to Enhance Proliferation and Differentiation of Normal Stem Cells via Activation of NRF2 Pathway: Review.Antioxidants (Basel, Switzerland) · 2025Review
- IL-6-mediated tumorigenicity and antioxidant state in squamous cell carcinoma cells are driven by CD109 via stabilization of IL-6 receptor-alpha and activation of STAT3/NRF2 pathway.Experimental hematology & oncology · 2025Article
- Article
- Regulation of ubiquitin-proteasome system and its relative pathways in pancreatic adenocarcinoma.BioImpacts : BI · 2025Review
- Pinitol Improves Diabetic Foot Ulcers in Streptozotocin-Induced Diabetes Rats Through Upregulation of Nrf2/HO-1 Signaling.Antioxidants (Basel, Switzerland) · 2024Article
- NRF2 in age-related musculoskeletal diseases: Role and treatment prospects.Genes & diseases · 2024Review
- Redox heterogeneity in mouse embryonic stem cells individualizes cell fate decisions.Developmental cell · 2024Article
- LIM-domain-only 4 (LMO4) enhances CD8Signal transduction and targeted therapy · 2024Article
- Tetramethylpyrazine Nitrone Promotes the Clearance of Alpha-Synuclein via Nrf2-Mediated Ubiquitin-Proteasome System Activation.Neuromolecular medicine · 2024Article
- Transcription Factor NRF2 in Shaping Myeloid Cell Differentiation and Function.Advances in experimental medicine and biology · 2024Review
- Proteasome Activators and Ageing: Restoring Proteostasis Using Small Molecules.Sub-cellular biochemistry · 2024Review
- Enhancement of porcine in vitro embryonic development through luteolin-mediated activation of the Nrf2/Keap1 signaling pathway.Journal of animal science and biotechnology · 2023Article
- Aging, NRF2, and TAU: A Perfect Match for Neurodegeneration?Antioxidants (Basel, Switzerland) · 2023Review
48 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 2 countries.
Funding
Abstract
Nuclear factor, erythroid 2-like 2 (Nrf2) is a master transcription factor for cellular defense against endogenous and exogenous stresses by regulating expression of many antioxidant and detoxification genes. Here, we show that Nrf2 acts as a key pluripotency gene and a regulator of proteasome activity in human embryonic stem cells (hESCs). Nrf2 expression is highly enriched in hESCs and dramatically decreases upon differentiation. Nrf2 inhibition impairs both the self-renewal ability of hESCs and re-establishment of pluripotency during cellular reprogramming. Nrf2 activation can delay differentiation. During early hESC differentiation, Nrf2 closely colocalizes with OCT4 and NANOG. As an underlying mechanism, our data show that Nrf2 regulates proteasome activity in hESCs partially through proteasome maturation protein (POMP), a proteasome chaperone, which in turn controls the proliferation of self-renewing hESCs, three germ layer differentiation and cellular reprogramming. Even modest proteasome inhibition skews the balance of early differentiation toward mesendoderm at the expense of an ectodermal fate by decreasing the protein level of cyclin D1 and delaying the degradation of OCT4 and NANOG proteins. Taken together, our findings suggest a new potential link between environmental stress and stemness with Nrf2 and the proteasome coordinately positioned as key mediators.
Indexed as
Identifiers
What OpenQuestion holds
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.