Molecular signatures distinguish senescent cells from inflammatory cells in aged mouse callus stromal cells
Cellular senescence plays important roles in age-related diseases, including musculoskeletal disorders. Senescent cells (SCs) exert a senescence-associated secretory phenotype (SASP) by producing SASP factors, some of which overlap with factors produced by inflammatory cells (Inf-Cs). However, the d...
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| Format: | Article |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1090049/full |
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| author | Jiatong Liu Xi Lin Andrew McDavid Yutiancheng Yang Hengwei Zhang Brendan F. Boyce Brendan F. Boyce Lianping Xing Lianping Xing |
| author_facet | Jiatong Liu Xi Lin Andrew McDavid Yutiancheng Yang Hengwei Zhang Brendan F. Boyce Brendan F. Boyce Lianping Xing Lianping Xing |
| author_sort | Jiatong Liu |
| collection | DOAJ |
| description | Cellular senescence plays important roles in age-related diseases, including musculoskeletal disorders. Senescent cells (SCs) exert a senescence-associated secretory phenotype (SASP) by producing SASP factors, some of which overlap with factors produced by inflammatory cells (Inf-Cs). However, the differences between SCs and Inf-Cs and how they interact with each other during fracture repair have not been well studied. Here, we analyzed single cell RNA sequencing data of aged mouse fracture callus stromal cells. We defined Inf-Cs as cells that express NF-κB Rela/Relb, SCs as cells that express the senescence genes, Cdkn1a, Cdkn2a or Cdkn2c, and inflammatory SCs (Inf-SCs) as cells that express both NF-κB and senescence genes. Differentially expressed genes and pathway analyses revealed that Inf-SCs and SCs had a similar gene expression profile and upregulated pathways that are related to DNA damage/oxidation-reduction and cellular senescence, while Inf-Cs expressed different gene signatures and pathways from SCs and Inf-SCs, mainly related to inflammation. Cellchat software analysis indicated that SCs and Inf-SCs are potential ligand-producing cells that affect Inf-Cs as target cells. Cell culture experiments demonstrated that SC conditioned medium promoted inflammatory gene expression by callus-derived mesenchymal progenitor cells, and Inf-Cs had reduced osteoblast differentiation capacity. In summary, we have identified three cell subclusters associated with inflammation and senescence in callus stromal cells, predicted potential effects of Inf-SCs and SCs on Inf-Cs by production of active ligands, and demonstrated that when mesenchymal progenitors acquire inflammatory phenotypes their osteogenic potential is reduced. |
| first_indexed | 2024-04-10T09:55:59Z |
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| id | doaj.art-f3556008dc5045ad96badff1926c5b72 |
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| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-10T09:55:59Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-f3556008dc5045ad96badff1926c5b722023-02-16T12:28:37ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-02-011410.3389/fendo.2023.10900491090049Molecular signatures distinguish senescent cells from inflammatory cells in aged mouse callus stromal cellsJiatong Liu0Xi Lin1Andrew McDavid2Yutiancheng Yang3Hengwei Zhang4Brendan F. Boyce5Brendan F. Boyce6Lianping Xing7Lianping Xing8Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, United StatesDepartment of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, United StatesBiostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY, United StatesDepartment of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, United StatesDepartment of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, United StatesDepartment of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, United StatesOrthopaedics and Rehabilitation, Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, United StatesDepartment of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, United StatesOrthopaedics and Rehabilitation, Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, United StatesCellular senescence plays important roles in age-related diseases, including musculoskeletal disorders. Senescent cells (SCs) exert a senescence-associated secretory phenotype (SASP) by producing SASP factors, some of which overlap with factors produced by inflammatory cells (Inf-Cs). However, the differences between SCs and Inf-Cs and how they interact with each other during fracture repair have not been well studied. Here, we analyzed single cell RNA sequencing data of aged mouse fracture callus stromal cells. We defined Inf-Cs as cells that express NF-κB Rela/Relb, SCs as cells that express the senescence genes, Cdkn1a, Cdkn2a or Cdkn2c, and inflammatory SCs (Inf-SCs) as cells that express both NF-κB and senescence genes. Differentially expressed genes and pathway analyses revealed that Inf-SCs and SCs had a similar gene expression profile and upregulated pathways that are related to DNA damage/oxidation-reduction and cellular senescence, while Inf-Cs expressed different gene signatures and pathways from SCs and Inf-SCs, mainly related to inflammation. Cellchat software analysis indicated that SCs and Inf-SCs are potential ligand-producing cells that affect Inf-Cs as target cells. Cell culture experiments demonstrated that SC conditioned medium promoted inflammatory gene expression by callus-derived mesenchymal progenitor cells, and Inf-Cs had reduced osteoblast differentiation capacity. In summary, we have identified three cell subclusters associated with inflammation and senescence in callus stromal cells, predicted potential effects of Inf-SCs and SCs on Inf-Cs by production of active ligands, and demonstrated that when mesenchymal progenitors acquire inflammatory phenotypes their osteogenic potential is reduced.https://www.frontiersin.org/articles/10.3389/fendo.2023.1090049/fullinflammationScRNA-seqagingfracturesenescence |
| spellingShingle | Jiatong Liu Xi Lin Andrew McDavid Yutiancheng Yang Hengwei Zhang Brendan F. Boyce Brendan F. Boyce Lianping Xing Lianping Xing Molecular signatures distinguish senescent cells from inflammatory cells in aged mouse callus stromal cells Frontiers in Endocrinology inflammation ScRNA-seq aging fracture senescence |
| title | Molecular signatures distinguish senescent cells from inflammatory cells in aged mouse callus stromal cells |
| title_full | Molecular signatures distinguish senescent cells from inflammatory cells in aged mouse callus stromal cells |
| title_fullStr | Molecular signatures distinguish senescent cells from inflammatory cells in aged mouse callus stromal cells |
| title_full_unstemmed | Molecular signatures distinguish senescent cells from inflammatory cells in aged mouse callus stromal cells |
| title_short | Molecular signatures distinguish senescent cells from inflammatory cells in aged mouse callus stromal cells |
| title_sort | molecular signatures distinguish senescent cells from inflammatory cells in aged mouse callus stromal cells |
| topic | inflammation ScRNA-seq aging fracture senescence |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1090049/full |
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