ArticleThe Journal of biological chemistry2019
Vitamin C-dependent lysine demethylase 6 (KDM6)-mediated demethylation promotes a chromatin state that supports the endothelial-to-hematopoietic transition.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
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- Identification of Trogocytosis as an Essential Limitation Factor in hPSC-derived CAR Macrophages.International journal of biological sciences · 2026Article
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- Human induced pluripotent stem cells derived neutrophils display strong anti-microbial potencies.Cell regeneration (London, England) · 2025Article
- H3K27me3-mediated epigenetic regulation in pluripotency maintenance and lineage differentiation.Cell insight · 2024Review
- HBO1 determines SMAD action in pluripotency and mesendoderm specification.Nucleic acids research · 2024Article
- Characterization of gene regulatory networks underlying key properties in human hematopoietic stem cell ontogeny.Cell regeneration (London, England) · 2024Article
- Large-scale generation of IL-12 secreting macrophages from human pluripotent stem cells for cancer therapy.Molecular therapy. Methods & clinical development · 2024Article
- Autophagy is essential for human myelopoiesis.Stem cell reports · 2024Article
- De Novo Generation of Human Hematopoietic Stem Cells from Pluripotent Stem Cells for Cellular Therapy.Cells · 2023Review
- Knockdown ofInternational journal of molecular sciences · 2022Article
- Vitamin C epigenetically controls osteogenesis and bone mineralization.Nature communications · 2022Article
- GFI1 regulates chromatin state essential in human endothelial-to-haematopoietic transition.Cell proliferation · 2022Article
- Coordination of EZH2 and SOX2 specifies human neural fate decision.Cell regeneration (London, England) · 2021Article
- Efficient derivation of human trophoblast stem cells from primed pluripotent stem cells.Science advances · 2021Article
- Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination.Nutrients · 2021Review
- The Functions of the Demethylase JMJD3 in Cancer.International journal of molecular sciences · 2021Review
- The Multiple Roles of Ascorbate in the Abiotic Stress Response of Plants: Antioxidant, Cofactor, and Regulator.Frontiers in plant science · 2021Review
- Emerging epigenetic therapeutics for myeloid leukemia: modulating demethylase activity with ascorbate.Haematologica · 2021Review
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Authors and funding
32 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hematopoietic stem cells (HSCs)/progenitor cells (HPCs) are generated from hemogenic endothelial cells (HECs) during the endothelial-to-hematopoietic transition (EHT); however, the underlying mechanism remains poorly understood. Here, using an array of approaches, including CRSPR/Cas9 gene knockouts, RNA-Seq, ChIP-Seq, ATAC-Seq etc., we report that vitamin C (Vc) is essential in HPC generation during human pluripotent stem cell (hPSC) differentiation in defined culture conditions. Mechanistically, we found that the endothelial cells generated in the absence of Vc fail to undergo the EHT because of an apparent failure in opening up genomic loci essential for hematopoiesis. Under Vc deficiency, these loci exhibited abnormal accumulation of histone H3 trimethylation at Lys-27 (H3K27me3), a repressive histone modification that arose because of lower activities of demethylases that target H3K27me3. Consistently, deletion of the two H3K27me3 demethylases, Jumonji domain-containing 3 (JMJD3 or KDM6B) and histone demethylase UTX (UTX or KDM6A), impaired HPC generation even in the presence of Vc. Furthermore, we noted that Vc and jmjd3 are also important for HSC generation during zebrafish development. Together, our findings reveal an essential role for Vc in the EHT for hematopoiesis, and identify KDM6-mediated chromatin demethylation as an important regulatory mechanism in hematopoietic cell differentiation.
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