TFPI from erythroblasts drives heme production in central macrophages promoting erythropoiesis in polycythemia.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38729948.
- Also identified by DOI 10.1038/s41467-024-48328-8 and PMC identifier 11087540.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Bleeding and thrombosis are known as common complications of polycythemia for a long time. However, the role of coagulation system in erythropoiesis is unclear. Here, we discover that an anticoagulant protein tissue factor pathway inhibitor (TFPI) plays an essential role in erythropoiesis via the control of heme biosynthesis in central macrophages. TFPI levels are elevated in erythroblasts of human erythroblastic islands with JAK2<sup>V617F</sup> mutation and hypoxia condition. Erythroid lineage-specific knockout TFPI results in impaired erythropoiesis through decreasing ferrochelatase expression and heme biosynthesis in central macrophages. Mechanistically, the TFPI interacts with thrombomodulin to promote the downstream ERK1/2-GATA1 signaling pathway to induce heme biosynthesis in central macrophages. Furthermore, TFPI blockade impairs human erythropoiesis in vitro, and normalizes the erythroid compartment in mice with polycythemia. These results show that erythroblast-derived TFPI plays an important role in the regulation of erythropoiesis and reveal an interplay between erythroblasts and central macrophages.
Medical subject headings
- Polycythemia
- Erythroblasts
- Erythropoiesis
- Heme
- Lipoproteins
- Macrophages
- GATA1 Transcription Factor