ArticleRedox biology2020
The NOTCH1-dependent HIF1α/VGLL4/IRF2BP2 oxygen sensing pathway triggers erythropoiesis terminal differentiation.
Article in Redox biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Adequacy of an Altitude Fitness Program (Living and Training) plus Intermittent Exposure to Hypoxia for Improving Hematological Biomarkers and Sports Performance of Elite Athletes: A Single-Blind Randomized Clinical Trial.International journal of environmental research and public health · 2022Trial
- Coupling Vgll4b/Yap-regulated posterior cell addition with anterior vacuolation enables robust notochord elongation.Development (Cambridge, England) · 2026Article
- Vestigial-like 4 Regulates Neurogenesis and Neural Crest Formation DuringJournal of developmental biology · 2026Article
- Tead1a Initiates Transcriptional Priming Through the TEAD1a/YAP-Notch1-Spi1/Cebpα Axis to Promote Neutrophil Fate.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Hippo signaling pathway as a therapeutic target in Alzheimer's disease.Molecular neurodegeneration · 2025Review
- Structural Variations Associated with Adaptation and Coat Color in Qinghai-Tibetan Plateau Cattle.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Malate initiates a proton-sensing pathway essential for pH regulation of inflammation.Signal transduction and targeted therapy · 2024Article
- MaternalFrontiers in cell and developmental biology · 2024Article
- VGLL4 promotes vascular endothelium specification via TEAD1 in the vascular organoids and human pluripotent stem cells-derived endothelium model.Cellular and molecular life sciences : CMLS · 2023Article
- RNA-seq and qRT-PCR analyses reveal the physiological response to acute hypoxia and reoxygenation inFrontiers in physiology · 2022Article
- Savior Siblings Might Rescue Fetal Lethality But Not Adult Lymphoma in Irf2bp2-Null Mice.Frontiers in immunology · 2022Article
- Using the Zebrafish as a Genetic Model to Study Erythropoiesis.International journal of molecular sciences · 2021Review
- Bayesian information sharing enhances detection of regulatory associations in rare cell types.Bioinformatics (Oxford, England) · 2021Article
- Intermittent not continuous hypoxia provoked haematological adaptations in healthy seniors: hypoxic pattern may hold the key.European journal of applied physiology · 2020Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia is widely considered as a limiting factor in vertebrate embryonic development, which requires adequate oxygen delivery for efficient energy metabolism, while nowadays some researches have revealed that hypoxia can induce stem cells so as to improve embryonic development. Erythroid differentiation is the oxygen delivery method employed by vertebrates at the very early step of embryo development, however, the mechanism how erythroid progenitor cell was triggered into mature erythrocyte is still not clear. In this study, after detecting the upregulation of vgll4b in response to oxygen levels, we generated vgll4b mutant zebrafish using CRISPR/Cas9, and verified the resulting impaired heme and dysfunctional erythroid terminal differentiation phenotype. Neither the vgll4b-deficient nor the γ-secretase inhibitor IX (DAPT)-adapted zebrafish were able to mediate HIF1α-induced heme generation. In addition, we showed that vgll4b mutant zebrafish were associated with an impaired erythroid phenotype, induced by the downregulation of alas2, which could be rescued by irf2bp2 depletion. Further mechanistic studies revealed that zebrafish VGLL4 sequesters IRF2BP2, thereby inhibiting its repression of alas2 expression and heme biosynthesis. These processes occur primarily via the VGLL4 TDU1 and IRF2BP2 ring finger domains. Our study also indicates that VGLL4 is a key player in the mediation of NOTCH1-dependent HIF1α-regulated erythropoiesis and can be sensitively regulated by oxygen concentrations. On the other hand, VGLL4 is a pivotal regulator of heme biosynthesis and erythroid terminal differentiation, which collectively improve oxygen metabolism.
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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.