ArticleBlood2019
Low iron promotes megakaryocytic commitment of megakaryocytic-erythroid progenitors in humans and mice.
Article in Blood, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 81 citations in OpenAlex.
- Effect of ferric citrate hydrate on fibroblast growth factor 23 and platelets in non-dialysis-dependent chronic kidney disease and non-chronic kidney disease patients with iron deficiency anemia.Clinical and experimental nephrology · 2024Trial
- Mechanisms of Thrombocytosis in Iron-Deficiency Anemia.European journal of haematology · 2026Review
- Serum erythropoietin level in cases of iron deficiency anemia with thrombocytosis: A cross-sectional study.Irish journal of medical science · 2026Article
- Serum erythropoietin level in cases of iron deficiency anemia with thrombocytosis: A cross-sectional study.Irish journal of medical science · 2026Article
- Platelet dysfunction in chronic kidney disease arises from bone marrow remodeling and megakaryocyte reprogramming.Blood advances · 2026Article
- Serum Iron and Its Relationship with Hematologic Parameters in Healthy Female Alpacas at Two Different Ages.Biological trace element research · 2026Article
- Mitochondrial iron transport via MFRN1 is required for erythroid cell cycle progression.Blood advances · 2025Article
- RBM15-MKL1 fusion protein promotes leukemia via m6A methylation and Wnt pathway activation.Blood · 2025Article
- Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling for Iron-Regulated Hematopoietic Stem and Progenitor Cells' Commitment toward Erythroid and Megakaryocytic Lineages.ACS pharmacology & translational science · 2025Article
- Haematometabolism rewiring in atherosclerotic cardiovascular disease.Nature reviews. Cardiology · 2025Review
- Iron trapping in macrophages reshapes the homeostasis of the haematopoietic system.British journal of haematology · 2025Article
- Dose-dependent effects of eltrombopag iron chelation on platelet formation.Blood vessels, thrombosis & hemostasis · 2025Article
- Transformer-based artificial intelligence on single-cell clinical data for homeostatic mechanism inference and rational biomarker discovery.medRxiv : the preprint server for health sciences · 2025Article
- Iron Deficiency Anemia.Advances in experimental medicine and biology · 2025Review
- Stem Cell Steal After Intravenous Iron: A Case of Transient Thrombocytopenia in Severe Iron Deficiency Anaemia.European journal of case reports in internal medicine · 2025Article
- CDK9 phosphorylates RUNX1 to promote megakaryocytic fate in megakaryocytic-erythroid progenitors.Blood · 2024Article
- Thrombocytosis and megakaryocyte changes associated with PRCA.Blood advances · 2024Article
- Tumor cell-released kynurenine biases MEP differentiation into megakaryocytes in individuals with cancer by activating AhR-RUNX1.Nature immunology · 2023Article
- Bone marrow sinusoidal endothelial cells are a site of Fgf23 upregulation in a mouse model of iron deficiency anemia.Blood advances · 2023Article
- SATB1 Chromatin Loops Regulate Megakaryocyte/Erythroid Progenitor Expansion by Facilitating HSP70 and GATA1 Induction.Stem cells (Dayton, Ohio) · 2023Article
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12 authors at 2 institutions in 1 country.
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Abstract
The mechanisms underlying thrombocytosis in patients with iron deficiency anemia remain unknown. Here, we present findings that support the hypothesis that low iron biases the commitment of megakaryocytic (Mk)-erythroid progenitors (MEPs) toward the Mk lineage in both human and mouse. In MEPs of transmembrane serine protease 6 knockout (Tmprss6-/-) mice, which exhibit iron deficiency anemia and thrombocytosis, we observed a Mk bias, decreased labile iron, and decreased proliferation relative to wild-type (WT) MEPs. Bone marrow transplantation assays suggest that systemic iron deficiency, rather than a local role for Tmprss6-/- in hematopoietic cells, contributes to the MEP lineage commitment bias observed in Tmprss6-/- mice. Nontransgenic mice with acquired iron deficiency anemia also show thrombocytosis and Mk-biased MEPs. Gene expression analysis reveals that messenger RNAs encoding genes involved in metabolic, vascular endothelial growth factor, and extracellular signal-regulated kinase (ERK) pathways are enriched in Tmprss6-/- vs WT MEPs. Corroborating our findings from the murine models of iron deficiency anemia, primary human MEPs exhibit decreased proliferation and Mk-biased commitment after knockdown of transferrin receptor 2, a putative iron sensor. Signal transduction analyses reveal that both human and murine MEP have lower levels of phospho-ERK1/2 in iron-deficient conditions compared with controls. These data are consistent with a model in which low iron in the marrow environment affects MEP metabolism, attenuates ERK signaling, slows proliferation, and biases MEPs toward Mk lineage commitment.
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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.