ArticleStem cells (Dayton, Ohio)2017
Zeb2 Regulates Cell Fate at the Exit from Epiblast State in Mouse Embryonic Stem Cells.
Article in Stem cells (Dayton, Ohio), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 58 citations in OpenAlex.
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- Cancer neuroscience: signaling pathways and new therapeutic strategies for cancer.Signal transduction and targeted therapy · 2026Review
- Specific Marker Gene Analysis for Primary Central Nervous System Lymphoma Based on Methylation Difference and Development of Detection Primers.Brain and behavior · 2025Article
- The Multifaceted Roles of Zinc Finger Proteins in Pluripotency and Reprogramming.International journal of molecular sciences · 2025Review
- Hypoxia-responsive zinc finger E-box-binding homeobox 2 (ZEB2) regulates a network of calcium-handling genes in the injured heart.Cardiovascular research · 2024Article
- Single-cell sequencing of the vermiform appendix during development identifies transcriptional relationships with appendicitis in preschool children.BMC medicine · 2024Article
- Lack of basic rationale in epithelial-mesenchymal transition and its related concepts.Cell & bioscience · 2024Review
- Identification of the DNA methylation signature of Mowat-Wilson syndrome.European journal of human genetics : EJHG · 2024Article
- Dynamic interplay of nuclear receptors in tumor cell plasticity and drug resistance: Shifting gears in malignant transformations and applications in cancer therapeutics.Cancer metastasis reviews · 2024Review
- Mowat-Wilson syndrome factor ZEB2 controls early formation of human neural crest through BMP signaling modulation.Stem cell reports · 2023Article
- Serum-Circulating microRNAs in Sporadic Inclusion Body Myositis.International journal of molecular sciences · 2023Article
- Article
- Endothelial Zeb2 preserves the hepatic angioarchitecture and protects against liver fibrosis.Cardiovascular research · 2022Article
- Article
- Conditional specification of endomesoderm.Cells & development · 2021Review
- Smart-RRBS for single-cell methylome and transcriptome analysis.Nature protocols · 2021Review
- Review
- Article
- Cardiomyocytes stimulate angiogenesis after ischemic injury in a ZEB2-dependent manner.Nature communications · 2021Article
- Zeb2 regulates the balance between retinal interneurons and Müller glia by inhibition of BMP-Smad signaling.Developmental biology · 2020Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In human embryonic stem cells (ESCs) the transcription factor Zeb2 regulates neuroectoderm versus mesendoderm formation, but it is unclear how Zeb2 affects the global transcriptional regulatory network in these cell-fate decisions. We generated Zeb2 knockout (KO) mouse ESCs, subjected them as embryoid bodies (EBs) to neural and general differentiation and carried out temporal RNA-sequencing (RNA-seq) and reduced representation bisulfite sequencing (RRBS) analysis in neural differentiation. This shows that Zeb2 acts preferentially as a transcriptional repressor associated with developmental progression and that Zeb2 KO ESCs can exit from their naïve state. However, most cells in these EBs stall in an early epiblast-like state and are impaired in both neural and mesendodermal differentiation. Genes involved in pluripotency, epithelial-to-mesenchymal transition (EMT), and DNA-(de)methylation, including Tet1, are deregulated in the absence of Zeb2. The observed elevated Tet1 levels in the mutant cells and the knowledge of previously mapped Tet1-binding sites correlate with loss-of-methylation in neural-stimulating conditions, however, after the cells initially acquired the correct DNA-methyl marks. Interestingly, cells from such Zeb2 KO EBs maintain the ability to re-adapt to 2i + LIF conditions even after prolonged differentiation, while knockdown of Tet1 partially rescues their impaired differentiation. Hence, in addition to its role in EMT, Zeb2 is critical in ESCs for exit from the epiblast state, and links the pluripotency network and DNA-methylation with irreversible commitment to differentiation. Stem Cells 2017;35:611-625.
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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.