ArticleCell communication and signaling : CCS2024
Megakaryocytic IGF1 coordinates activation and ferroptosis to safeguard hematopoietic stem cell regeneration after radiation injury.
Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Advances in the Regulation of Hematopoietic Homeostasis by Programmed Cell Death Under Radiation Conditions.Stem cell reviews and reports · 2025Pooled it
- Breaking through the radiation dilemma: development and clinical translation of anti-radiation drugs.Pharmaceutical science advances · 2026Review
- Radiosensitive HSPC Subsets Define Early Hematopoietic Injury and Enable H-ARS Therapeutic Screening.Current issues in molecular biology · 2026Article
- Article
- Radiomitigators: Breakthroughs in Post-Radiation Recovery.Antioxidants (Basel, Switzerland) · 2026Review
- Targeting Leukopoiesis: Pharmacological and Biotechnological Strategies for the Treatment of Leukopenia.Biomedicines · 2026Review
- Megakaryocytic TGFβ1 orchestrates osteogenesis of LepRExperimental & molecular medicine · 2026Article
- Potential Mechanisms of Exercise-Mediated Ferroptosis Regulation in Central Nervous System Diseases.Molecular neurobiology · 2025Review
- From mitochondrial dysregulation to ferroptosis: Exploring new strategies and challenges in radioimmunotherapy (Review).International journal of oncology · 2025Review
- Ferulic Acid Promotes Hematopoietic Stem Cell Maintenance in Homeostasis and Injury Through Diminishing Ferroptosis Susceptibility.Antioxidants (Basel, Switzerland) · 2025Article
- Programmed cell death regulates hematopoietic cell homeostasis under radiation conditions.Stem cell research & therapy · 2025Article
- New insights into the generation and function of megakaryocytes in health and disease.Haematologica · 2025Review
- DSUP modified mesenchymal stem cells exert significant radiation protective effect by enhancing the hematopoietic niche.Stem cell research & therapy · 2025Article
- Functional Equivalence of Insulin and IGF-1 in the In Vitro Culture of Chicken Primordial Germ Cells.Genes · 2025Article
- Adipose-derived stem cells alleviate radiation-induced muscle fibrosis by promoting muscle regeneration.Frontiers in cell and developmental biology · 2025Article
- Insights into ionizing radiation-induced bone marrow hematopoietic stem cell injury.Stem cell research & therapy · 2024Review
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Authors and funding
15 authors.
Funding
Abstract
backgroundHematopoietic stem cell (HSC) regeneration underlies hematopoietic recovery from myelosuppression, which is a life-threatening side effect of cytotoxicity. HSC niche is profoundly disrupted after myelosuppressive injury, while if and how the niche is reshaped and regulates HSC regeneration are poorly understood.
methodsA mouse model of radiation injury-induced myelosuppression was built by exposing mice to a sublethal dose of ionizing radiation. The dynamic changes in the number, distribution and functionality of HSCs and megakaryocytes were determined by flow cytometry, immunofluorescence, colony assay and bone marrow transplantation, in combination with transcriptomic analysis. The communication between HSCs and megakaryocytes was determined using a coculture system and adoptive transfer. The signaling mechanism was investigated both in vivo and in vitro, and was consolidated using megakaryocyte-specific knockout mice and transgenic mice.
resultsMegakaryocytes become a predominant component of HSC niche and localize closer to HSCs after radiation injury. Meanwhile, transient insulin-like growth factor 1 (IGF1) hypersecretion is predominantly provoked in megakaryocytes after radiation injury, whereas HSCs regenerate paralleling megakaryocytic IGF1 hypersecretion. Mechanistically, HSCs are particularly susceptible to megakaryocytic IGF1 hypersecretion, and mTOR downstream of IGF1 signaling not only promotes activation including proliferation and mitochondrial oxidative metabolism of HSCs, but also inhibits ferritinophagy to restrict HSC ferroptosis. Consequently, the delicate coordination between proliferation, mitochondrial oxidative metabolism and ferroptosis ensures functional HSC expansion after radiation injury. Importantly, punctual IGF1 administration simultaneously promotes HSC regeneration and hematopoietic recovery after radiation injury, representing a superior therapeutic approach for myelosuppression.
conclusionsOur study identifies megakaryocytes as a last line of defense against myelosuppressive injury and megakaryocytic IGF1 as a novel niche signal safeguarding HSC regeneration.
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