Spatiotemporal Analysis of Mesenchymal Stem Cells Fate Determination by Inflammatory Niche Following Soft Tissue Injury at a Single‐Cell Level
Abstract Heterotopic ossification (HO), often arising in response to traumatic challenges, results from the aberrant osteochondral differentiation of mesenchymal stem cells (MSCs). Nevertheless, the impact of trauma‐induced inflammatory exposure on MSC fate determination remains ambiguous. In this s...
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Wiley
2024-11-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202310282 |
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| author | Chen Kan Zhenya Tan Haitao Wang Wei Wang Jiazhao Yang Ya Zhang Xiaoling Lu Qirong Cheng Lanyi Chai Chao Peng Jicheng Zhu Chenghang Zhu Hailin Wang Li Zhan Keqiong Lin Yakun Liu Lingqiang Zhang Haitao Fan Hong Zheng |
| author_facet | Chen Kan Zhenya Tan Haitao Wang Wei Wang Jiazhao Yang Ya Zhang Xiaoling Lu Qirong Cheng Lanyi Chai Chao Peng Jicheng Zhu Chenghang Zhu Hailin Wang Li Zhan Keqiong Lin Yakun Liu Lingqiang Zhang Haitao Fan Hong Zheng |
| author_sort | Chen Kan |
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| description | Abstract Heterotopic ossification (HO), often arising in response to traumatic challenges, results from the aberrant osteochondral differentiation of mesenchymal stem cells (MSCs). Nevertheless, the impact of trauma‐induced inflammatory exposure on MSC fate determination remains ambiguous. In this study, the cellular diversity within inflammatory lesions is elucidated, comprising MSCs and several innate and adaptive immune cells. It is observed that quiescent MSCs transition into cycling MSCs, subsequently giving rise to chondrogenic (cMSC) and/or osteogenic (oMSC) lineages within the inflammatory microenvironment following muscle or tendon injuries, as revealed through single‐cell RNA sequencing (scRNA‐seq), spatial transcriptome and lineage tracing analysis. Moreover, these investigations demonstrate that neutrophils and natural killer (NK) cells enhance transition of quiescent MSCs into cycling MSCs, which is also controlled by M1 macrophages, a subpopulation of macrophages can also stimulate cMSC and oMSC production from cycling MSCs. Additionally, M2 macrophages, CD4+ and CD8+ T lymphocytes are found to promote chondrogenesis. Further analysis demonstrates that immune cells promotes the activation of signaling transducers and activators of transcription (STAT) pathway and phosphoinositide 3 (PI3K)/protein kinase B (AKT) pathway in MSC proliferation and osteochondral progenitors’ production, respectively. These findings highlight the dynamics of MSC fate within the inflammatory lesion and unveil the molecular landscape of osteoimmunological interactions, which holds promise for advancing HO treatment. |
| format | Article |
| id | doaj-art-a594a89bb0ee4576941a57a230c1edf0 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj-art-a594a89bb0ee4576941a57a230c1edf02024-11-20T19:25:40ZengWileyAdvanced Science2198-38442024-11-011143n/an/a10.1002/advs.202310282Spatiotemporal Analysis of Mesenchymal Stem Cells Fate Determination by Inflammatory Niche Following Soft Tissue Injury at a Single‐Cell LevelChen Kan0Zhenya Tan1Haitao Wang2Wei Wang3Jiazhao Yang4Ya Zhang5Xiaoling Lu6Qirong Cheng7Lanyi Chai8Chao Peng9Jicheng Zhu10Chenghang Zhu11Hailin Wang12Li Zhan13Keqiong Lin14Yakun Liu15Lingqiang Zhang16Haitao Fan17Hong Zheng18Department of Pathophysiology School of Basic Medical Sciences Anhui Medical University Hefei 230032 ChinaDepartment of Pathophysiology School of Basic Medical Sciences Anhui Medical University Hefei 230032 ChinaDepartment of Physiology and Biomedical Engineering Mayo Clinic Rochester MN 55905 USADepartment of Pathophysiology School of Basic Medical Sciences Anhui Medical University Hefei 230032 ChinaDepartment of Orthopedics The First Affiliated Hospital of USTC Hefei 230001 ChinaDepartment of Pathophysiology School of Basic Medical Sciences Anhui Medical University Hefei 230032 ChinaDepartment of Pathophysiology School of Basic Medical Sciences Anhui Medical University Hefei 230032 ChinaDepartment of Pathophysiology School of Basic Medical Sciences Anhui Medical University Hefei 230032 ChinaDepartment of Pathophysiology School of Basic Medical Sciences Anhui Medical University Hefei 230032 ChinaDepartment of Pathophysiology School of Basic Medical Sciences Anhui Medical University Hefei 230032 ChinaDepartment of Pathophysiology School of Basic Medical Sciences Anhui Medical University Hefei 230032 ChinaDepartment of Pathophysiology School of Basic Medical Sciences Anhui Medical University Hefei 230032 ChinaDepartment of Pathophysiology School of Basic Medical Sciences Anhui Medical University Hefei 230032 ChinaDepartment of Pathophysiology School of Basic Medical Sciences Anhui Medical University Hefei 230032 ChinaDepartment of Pathophysiology School of Basic Medical Sciences Anhui Medical University Hefei 230032 ChinaDepartment of Pathophysiology School of Basic Medical Sciences Anhui Medical University Hefei 230032 ChinaState Key Laboratory of Medical Proteomics National Center for Protein Sciences (Beijing) Beijing Institute of Lifeomics Beijing 100850 ChinaDepartment of Orthopedics The First Affiliated Hospital of Ningbo University Ningbo 315010 ChinaDepartment of Pathophysiology School of Basic Medical Sciences Anhui Medical University Hefei 230032 ChinaAbstract Heterotopic ossification (HO), often arising in response to traumatic challenges, results from the aberrant osteochondral differentiation of mesenchymal stem cells (MSCs). Nevertheless, the impact of trauma‐induced inflammatory exposure on MSC fate determination remains ambiguous. In this study, the cellular diversity within inflammatory lesions is elucidated, comprising MSCs and several innate and adaptive immune cells. It is observed that quiescent MSCs transition into cycling MSCs, subsequently giving rise to chondrogenic (cMSC) and/or osteogenic (oMSC) lineages within the inflammatory microenvironment following muscle or tendon injuries, as revealed through single‐cell RNA sequencing (scRNA‐seq), spatial transcriptome and lineage tracing analysis. Moreover, these investigations demonstrate that neutrophils and natural killer (NK) cells enhance transition of quiescent MSCs into cycling MSCs, which is also controlled by M1 macrophages, a subpopulation of macrophages can also stimulate cMSC and oMSC production from cycling MSCs. Additionally, M2 macrophages, CD4+ and CD8+ T lymphocytes are found to promote chondrogenesis. Further analysis demonstrates that immune cells promotes the activation of signaling transducers and activators of transcription (STAT) pathway and phosphoinositide 3 (PI3K)/protein kinase B (AKT) pathway in MSC proliferation and osteochondral progenitors’ production, respectively. These findings highlight the dynamics of MSC fate within the inflammatory lesion and unveil the molecular landscape of osteoimmunological interactions, which holds promise for advancing HO treatment.https://doi.org/10.1002/advs.202310282heterotopic ossificationinflammatory microenvironmentmesenchymal stem cellsosteoimmunology |
| spellingShingle | Chen Kan Zhenya Tan Haitao Wang Wei Wang Jiazhao Yang Ya Zhang Xiaoling Lu Qirong Cheng Lanyi Chai Chao Peng Jicheng Zhu Chenghang Zhu Hailin Wang Li Zhan Keqiong Lin Yakun Liu Lingqiang Zhang Haitao Fan Hong Zheng Spatiotemporal Analysis of Mesenchymal Stem Cells Fate Determination by Inflammatory Niche Following Soft Tissue Injury at a Single‐Cell Level Advanced Science heterotopic ossification inflammatory microenvironment mesenchymal stem cells osteoimmunology |
| title | Spatiotemporal Analysis of Mesenchymal Stem Cells Fate Determination by Inflammatory Niche Following Soft Tissue Injury at a Single‐Cell Level |
| title_full | Spatiotemporal Analysis of Mesenchymal Stem Cells Fate Determination by Inflammatory Niche Following Soft Tissue Injury at a Single‐Cell Level |
| title_fullStr | Spatiotemporal Analysis of Mesenchymal Stem Cells Fate Determination by Inflammatory Niche Following Soft Tissue Injury at a Single‐Cell Level |
| title_full_unstemmed | Spatiotemporal Analysis of Mesenchymal Stem Cells Fate Determination by Inflammatory Niche Following Soft Tissue Injury at a Single‐Cell Level |
| title_short | Spatiotemporal Analysis of Mesenchymal Stem Cells Fate Determination by Inflammatory Niche Following Soft Tissue Injury at a Single‐Cell Level |
| title_sort | spatiotemporal analysis of mesenchymal stem cells fate determination by inflammatory niche following soft tissue injury at a single cell level |
| topic | heterotopic ossification inflammatory microenvironment mesenchymal stem cells osteoimmunology |
| url | https://doi.org/10.1002/advs.202310282 |
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