ArticleEMBO reports2023
Multinucleation resets human macrophages for specialized functions at the expense of their identity.
Article in EMBO reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- HIGH DOSE GAMMAHERPESVIRUS INFECTION IN MACROPHAGES RESULTS IN INFLAMMATORY MULTIMODAL CELL DEATH.bioRxiv : the preprint server for biology · 2026Article
- Transcriptomic and lipidomic analysis of the cryptococcal lung granuloma reveals macrophage boundary programs and sphingolipid remodeling.Nature communications · 2026Article
- M-CSF priming enhances the efficiency and reproducibility of hiPSC-derived osteoclast differentiation and pharmacological responsiveness to anti-resorptive agents.Scientific reports · 2026Article
- Distinct transcriptional and epigenomic programs define Hofbauer cells in term placenta.JCI insight · 2026Article
- Plasma membrane damage by environmental materials enhances cell-cell fusion and impairs defense functions of macrophages.Frontiers in immunology · 2026Article
- Polyploidy promotes transformation of epithelial cells into nonprofessional phagocytes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Multinucleated giant cells are hallmarks of ovarian aging with unique immune and degradation-associated molecular signatures.PLoS biology · 2025Article
- Identification of Programmed Cell Death-related Biomarkers for the Potential Diagnosis and Treatment of Osteoporosis.Endocrine, metabolic & immune disorders drug targets · 2025Article
- Cell fusion dynamics: mechanisms of multinucleation in osteoclasts and macrophages.Inflammation and regeneration · 2024Review
- Review
- The immune regulatory function of B7-H3 in malignancy: spotlight on the IFN-STAT1 axis and regulation of tumor-associated macrophages.Immunologic research · 2024Review
- Multinucleation resets human macrophages for specialized functions at the expense of their identity.EMBO reports · 2023Article
- The protective role of CD73 in periodontitis: preventing hyper-inflammatory fibroblasts and driving osteoclast energy metabolism.Frontiers in oral health · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
Abstract
Macrophages undergo plasma membrane fusion and cell multinucleation to form multinucleated giant cells (MGCs) such as osteoclasts in bone, Langhans giant cells (LGCs) as part of granulomas or foreign-body giant cells (FBGCs) in reaction to exogenous material. How multinucleation per se contributes to functional specialization of mature mononuclear macrophages remains poorly understood in humans. Here, we integrate comparative transcriptomics with functional assays in purified mature mononuclear and multinucleated human osteoclasts, LGCs and FBGCs. Strikingly, in all three types of MGCs, multinucleation causes a pronounced downregulation of macrophage identity. We show enhanced lysosome-mediated intracellular iron homeostasis promoting MGC formation. The transition from mononuclear to multinuclear state is accompanied by cell specialization specific to each polykaryon. Enhanced phagocytic and mitochondrial function associate with FBGCs and osteoclasts, respectively. Moreover, human LGCs preferentially express B7-H3 (CD276) and can form granuloma-like clusters in vitro, suggesting that their multinucleation potentiates T cell activation. These findings demonstrate how cell-cell fusion and multinucleation reset human macrophage identity as part of an advanced maturation step that confers MGC-specific functionality.
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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.