ArticleThe EMBO journal2011
A regulatory circuitry comprised of miR-302 and the transcription factors OCT4 and NR2F2 regulates human embryonic stem cell differentiation.
Article in The EMBO journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 1 of them a synthesis that pooled it.
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
111 citing papers in PubMed, 1 synthesis or guideline pooled it, 211 citations in OpenAlex.
- Multitrait meta-analysis identified genomic regions associated with sexual precocity in tropical beef cattle.Journal of animal science · 2018Pooled it
- Cranial neural crest shortage leads to extensive craniofacial anomalies in mice mutant for the NR2F1/2 nuclear receptors.Developmental biology · 2026Article
- The harmonies played by miR-302/367 cluster in pluripotency, reprogramming, and rejuvenation.Stem cells translational medicine · 2026Review
- Role of COUP‑TFII in cardiovascular diseases and colorectal cancer: Insights into the molecular mechanisms and clinical relevance (Review).Molecular medicine reports · 2025Review
- Splicing to keep splicing: A feedback system for cellular homeostasis and state transition.Clinical and translational medicine · 2025Review
- Stem Cell-Derived Exosomal MicroRNAs as Novel Potential Approach for Multiple Sclerosis Treatment.Cellular and molecular neurobiology · 2024Review
- NANOG controls testicular germ cell tumour stemness through regulation of MIR9-2.Stem cell research & therapy · 2024Article
- COUP-TFII regulates early bipotential gonad signaling and commitment to ovarian progenitors.Cell & bioscience · 2024Article
- Article
- Human Embryonic Stem-Cell-Derived Exosomes Repress NLRP3 Inflammasome to Alleviate Pyroptosis in Nucleus Pulposus Cells by Transmitting miR-302c.International journal of molecular sciences · 2023Article
- An epigenetic switch controls an alternative NR2F2 isoform that unleashes a metastatic program in melanoma.Nature communications · 2023Article
- Non-coding RNAs: key regulators of reprogramming, pluripotency, and cardiac cell specification with therapeutic perspective for heart regeneration.Cardiovascular research · 2022Review
- A single allele of the hsa-miR-302/367 cluster maintains human pluripotent stem cells.Regenerative therapy · 2022Article
- Regulation of Oct4 in stem cells and neural crest cells.Birth defects research · 2022Review
- The Role of microRNAs in the Gonocyte Theory as Target of Malignancy: Looking for Potential Diagnostic Biomarkers.International journal of molecular sciences · 2022Review
- Isoforms of the orphan nuclear receptor COUP‑TFII differentially modulate pancreatic cancer progression.International journal of oncology · 2022Article
- Inter-regulatory role of microRNAs in interaction between viruses and stem cells.World journal of stem cells · 2021Review
- SETD4 in the Proliferation, Migration, Angiogenesis, Myogenic Differentiation and Genomic Methylation of Bone Marrow Mesenchymal Stem Cells.Stem cell reviews and reports · 2021Article
- Expression of the miR-302/367 microRNA cluster is regulated by a conserved long non-coding host-gene.Scientific reports · 2021Article
- Mapping germ-layer specification preventing genes in hPSCs via genome-scale CRISPR screening.iScience · 2021Article
51 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
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple levels of control are in play to regulate pluripotency and differentiation in human embryonic stem cells (hESCs). At the transcriptional level, the core factors OCT4, NANOG and SOX2 form a positive autoregulatory loop that is pivotal for maintaining the undifferentiated state. At the post-transcriptional level, microRNAs (miRNAs) belonging to the miR-302 family are emerging as key players in the control of proliferation and cell fate determination during differentiation. Here, we show that the transcriptional factors OCT4 and NR2F2 (COUP-TFII) and the miRNA miR-302 are linked in a regulatory circuitry that critically regulate both pluripotency and differentiation in hESCs. In the undifferentiated state, both OCT4 and the OCT4-induced miR-302 directly repress NR2F2 at the transcriptional and post-transcriptional level, respectively. Conversely, NR2F2 directly inhibits OCT4 during differentiation, triggering a positive feedback loop for its own expression. In addition, we show that regulation of NR2F2 activity itself relies on alternative splicing and transcriptional start site choice to generate a full-length transcriptionally active isoform and shorter variants, which enhance the activity of the long isoform. During hESC differentiation, NR2F2 is first detected at the earliest steps of neural induction and thus is among the earliest human embryonic neural markers. Finally, our functional analysis points to a crucial role for NR2F2 in the activation of neural genes during early differentiation in humans. These findings introduce a new molecular player in the context of early embryonic stem cell state and cell fate determination in humans.
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.