Single-cell transcriptomic analysis identifies systemic immunosuppressive myeloid cells and local monocytes/macrophages as key regulators in polytrauma-induced immune dysregulation
Abstract Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges. Although immune responses significantly influence fracture healing post-polytrauma, the cellular and molecular underpinnings of polytrauma-induced immune dysregulation require further inves...
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| Format: | Article |
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Nature Publishing Group
2025-07-01
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| Series: | Bone Research |
| Online Access: | https://doi.org/10.1038/s41413-025-00444-x |
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| author | Drishti Maniar M. Cole Keenum Casey E. Vantucci Tyler Guyer Paramita Chatterjee Kelly Leguineche Kaitlyn Cheung Robert E. Guldberg Krishnendu Roy |
| author_facet | Drishti Maniar M. Cole Keenum Casey E. Vantucci Tyler Guyer Paramita Chatterjee Kelly Leguineche Kaitlyn Cheung Robert E. Guldberg Krishnendu Roy |
| author_sort | Drishti Maniar |
| collection | DOAJ |
| description | Abstract Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges. Although immune responses significantly influence fracture healing post-polytrauma, the cellular and molecular underpinnings of polytrauma-induced immune dysregulation require further investigation. While previous studies examined either injury site tissue or systemic tissue (peripheral blood), our study uniquely investigated both systemic and local immune cells at the same time to better understand polytrauma-induced immune dysregulation and associated impaired bone healing. Using single-cell RNA sequencing (scRNA-seq) in a rat polytrauma model, we analyzed blood, bone marrow, and the local defect soft tissue to identify potential cellular and molecular targets involved in immune dysregulation. We identified a trauma-associated immunosuppressive myeloid (TIM) cell population that drives systemic immune dysregulation, immunosuppression, and potentially impaired bone healing. We found CD1d as a global marker for TIM cells in polytrauma. In the local defect tissue, we observed Spp1 + monocytes/macrophages mediating inflammatory, fibrotic, and impaired adaptive immune responses. Finally, our findings highlighted increased signaling via Anxa1-Fpr2 and Spp1-Cd44 axes. This comprehensive analysis enhances our understanding of immune dysregulation-mediated nonunion following traumatic injury and provides biomarkers that could function as treatment targets. |
| format | Article |
| id | doaj-art-e9f8fbd9513a41ad84f4867465570c30 |
| institution | Kabale University |
| issn | 2095-6231 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Bone Research |
| spelling | doaj-art-e9f8fbd9513a41ad84f4867465570c302025-08-20T03:45:51ZengNature Publishing GroupBone Research2095-62312025-07-0113111510.1038/s41413-025-00444-xSingle-cell transcriptomic analysis identifies systemic immunosuppressive myeloid cells and local monocytes/macrophages as key regulators in polytrauma-induced immune dysregulationDrishti Maniar0M. Cole Keenum1Casey E. Vantucci2Tyler Guyer3Paramita Chatterjee4Kelly Leguineche5Kaitlyn Cheung6Robert E. Guldberg7Krishnendu Roy8Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityDepartment of Bioengineering, University of OregonParker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of TechnologyDepartment of Bioengineering, University of OregonWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityDepartment of Bioengineering, University of OregonWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityAbstract Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges. Although immune responses significantly influence fracture healing post-polytrauma, the cellular and molecular underpinnings of polytrauma-induced immune dysregulation require further investigation. While previous studies examined either injury site tissue or systemic tissue (peripheral blood), our study uniquely investigated both systemic and local immune cells at the same time to better understand polytrauma-induced immune dysregulation and associated impaired bone healing. Using single-cell RNA sequencing (scRNA-seq) in a rat polytrauma model, we analyzed blood, bone marrow, and the local defect soft tissue to identify potential cellular and molecular targets involved in immune dysregulation. We identified a trauma-associated immunosuppressive myeloid (TIM) cell population that drives systemic immune dysregulation, immunosuppression, and potentially impaired bone healing. We found CD1d as a global marker for TIM cells in polytrauma. In the local defect tissue, we observed Spp1 + monocytes/macrophages mediating inflammatory, fibrotic, and impaired adaptive immune responses. Finally, our findings highlighted increased signaling via Anxa1-Fpr2 and Spp1-Cd44 axes. This comprehensive analysis enhances our understanding of immune dysregulation-mediated nonunion following traumatic injury and provides biomarkers that could function as treatment targets.https://doi.org/10.1038/s41413-025-00444-x |
| spellingShingle | Drishti Maniar M. Cole Keenum Casey E. Vantucci Tyler Guyer Paramita Chatterjee Kelly Leguineche Kaitlyn Cheung Robert E. Guldberg Krishnendu Roy Single-cell transcriptomic analysis identifies systemic immunosuppressive myeloid cells and local monocytes/macrophages as key regulators in polytrauma-induced immune dysregulation Bone Research |
| title | Single-cell transcriptomic analysis identifies systemic immunosuppressive myeloid cells and local monocytes/macrophages as key regulators in polytrauma-induced immune dysregulation |
| title_full | Single-cell transcriptomic analysis identifies systemic immunosuppressive myeloid cells and local monocytes/macrophages as key regulators in polytrauma-induced immune dysregulation |
| title_fullStr | Single-cell transcriptomic analysis identifies systemic immunosuppressive myeloid cells and local monocytes/macrophages as key regulators in polytrauma-induced immune dysregulation |
| title_full_unstemmed | Single-cell transcriptomic analysis identifies systemic immunosuppressive myeloid cells and local monocytes/macrophages as key regulators in polytrauma-induced immune dysregulation |
| title_short | Single-cell transcriptomic analysis identifies systemic immunosuppressive myeloid cells and local monocytes/macrophages as key regulators in polytrauma-induced immune dysregulation |
| title_sort | single cell transcriptomic analysis identifies systemic immunosuppressive myeloid cells and local monocytes macrophages as key regulators in polytrauma induced immune dysregulation |
| url | https://doi.org/10.1038/s41413-025-00444-x |
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