ArticleLeukemia2017
Estrogen promotes megakaryocyte polyploidization via estrogen receptor beta-mediated transcription of GATA1.
Article in Leukemia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Apoptosis-resistant megakaryocytes produce large and hyperreactive platelets in response to radiation injury.Military Medical Research · 2023Trial
- Platelet-derived microparticles induce CD8Experimental & molecular medicine · 2026Article
- Cold exposure aggravates vein occlusion through non-shivering thermogenesis-induced thrombocytopoiesis.Cell research · 2026Article
- Platelet Reactivity and Sex Differences: Clinical Implications for Women.Circulation research · 2026Review
- A systems herbal-to-molecule and transcriptomic strategy identifies emodin as an ESR1-targeting phytochemical driving thrombopoiesis.Chinese medicine · 2026Article
- Demographic diversity in platelet function and response to antiplatelet therapy.Trends in pharmacological sciences · 2025Review
- Article
- Megakaryocytic IGF1 coordinates activation and ferroptosis to safeguard hematopoietic stem cell regeneration after radiation injury.Cell communication and signaling : CCS · 2024Article
- Genistin: A Novel Estrogen Analogue Targeting ERβ to Alleviate Thrombocytopenia.International journal of biological sciences · 2024Article
- Application and investigation of thrombopoiesis-stimulating agents in the treatment of thrombocytopenia.Therapeutic advances in hematology · 2023Review
- Phosphate Metabolic Inhibition Contributes to Irradiation-Induced Myelosuppression through Dampening Hematopoietic Stem Cell Survival.Nutrients · 2022Article
- Rheumatoid arthritis, systemic lupus erythematosus and primary Sjögren's syndrome shared megakaryocyte expansion in peripheral blood.Annals of the rheumatic diseases · 2022Article
- Protective role of estrogen against excessive erythrocytosis in Monge's disease.Experimental & molecular medicine · 2021Article
- Induction of cell death and modulation of Annexin A1 by phytoestrogens in human leukemic cell lines.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2021Article
- Lysyl oxidase inhibition in primary myelofibrosis: A renewed strategy.Archives of stem cell and therapy · 2020Article
- Platelet-derived microparticles enhance megakaryocyte differentiation and platelet generation via miR-1915-3p.Nature communications · 2020Article
- Reprogramming of Mesothelial-Mesenchymal Transition in Chronic Peritoneal Diseases by Estrogen Receptor Modulation and TGF-β1 Inhibition.International journal of molecular sciences · 2020Review
- Review
- Effects of Estrogens on Platelets and Megakaryocytes.International journal of molecular sciences · 2019Review
- The Roles of Cholesterol and Its Metabolites in Normal and Malignant Hematopoiesis.Frontiers in endocrinology · 2019Review
Corrections and comments
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Estrogen is reported to be involved in thrombopoiesis and the disruption of its signaling may cause myeloproliferative disease, yet the underlying mechanisms remain largely unknown. GATA-binding factor 1 (GATA1) is a key regulator of megakaryocyte (MK) differentiation and its deficiency will lead to megakaryoblastic leukemia. Here we show that estrogen can dose-dependently promote MK polyploidization and maturation via activation of estrogen receptor beta (ERβ), accompanied by a significant upregulation of GATA1. Chromatin immunoprecipitation and a dual luciferase assay demonstrate that ERβ can directly bind the promoter region of GATA1 and activate its transcription. Steroid receptor coactivator 3 (SRC3) is involved in ERβ-mediated GATA1 transcription. The deficiency of ERβ or SRC3, similar to the inhibition of GATA1, leads to the impediment of estrogen-induced MK polyploidization and platelet production. Further investigations reveal that signal transducer and activator of transcription 1 signaling pathway downstream of GATA1 has a crucial role in estrogen-induced MK polyploidization, and ERβ-mediated GATA1 upregulation subsequently enhances nuclear factor erythroid-derived 2 expression, thereby promoting proplatelet formation and platelet release. Our study provides a deep insight into the molecular mechanisms of estrogen signaling in regulating thrombopoiesis and the pathogenesis of ER deficiency-related leukemia.
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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.