Endogenous spermidine biosynthesis contributes to fetal liver megakaryopoiesis and platelet production in mice.

Authors

Xing Liu, Meijuan Xia, Jiaojiao Guo, Liang Zhao, Yezi Ma, Long Li, Pei Su, Cuicui Liu, Fei Wang, Jiaxi Zhou, Wen Zhou, Hongtao Wang

Published in

Platelets. Volume 37. Issue 1. Pages 2714075. Epub Sep 02, 2026.

Abstract

Metabolic regulation is increasingly recognized as an important determinant of megakaryocyte development and platelet production, yet the metabolite-level characteristics of primary megakaryocytes from distinct developmental stages and tissue origins remain incompletely defined. Here, using microscale targeted metabolomics, we profiled primary megakaryocytes isolated from mouse liver and bone marrow. This analysis revealed distinct metabolomic profiles between the two megakaryocyte populations and identified spermidine and lysine as metabolites enriched in liver-derived megakaryocytes. Functional analyses showed that spermidine, but not lysine, promoted fetal liver-derived megakaryocyte generation and platelet-like particle formation in vitro, whereas these effects were not observed in adult bone marrow-derived cultures under the tested conditions. Maternal dietary spermidine supplementation increased fetal liver megakaryocyte generation and fetal platelet production in vivo, with limited detectable effects on megakaryopoiesis in the maternal bone marrow. Single-cell transcriptomic analysis and pharmacological perturbation further linked endogenous spermidine biosynthesis to fetal liver megakaryopoiesis. Inhibition of Odc1 or Amd1 reduced intracellular spermidine levels, impaired fetal liver-derived megakaryocyte differentiation and platelet-like particle formation, and exogenous spermidine partially rescued DFMO-induced defects. Together, these findings define distinct metabolic features of mouse liver- and bone marrow-derived megakaryocytes and support a role for endogenous spermidine biosynthesis in fetal liver megakaryopoiesis and platelet production.

PMID:
42683580
Bibliographic data and abstract were imported from PubMed on 02 Sep 2026.

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