Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions
A number of human diseases, such as arthritis and atherosclerosis, include characteristic pathology in specific anatomical locations. Here we show transcriptomic differences in synovial fibroblasts from different joint locations and that HOX gene signatures reflect the joint-specific origins of mous...
| Main Authors: | , , , , , , , , , , , , , , |
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| Formato: | Journal article |
| Publicado em: |
Nature Publishing Group
2017
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| _version_ | 1826304466235686912 |
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| author | Frank-Bertoncelj, M Trenkmann, M Klein, K Karouzakis, E Rehrauer, H Bratus, A Kolling, C Armaka, M Filer, A Michel, BA Gay, RE Buckley, CD Kollias, G Gay, S Ospelt, C |
| author_facet | Frank-Bertoncelj, M Trenkmann, M Klein, K Karouzakis, E Rehrauer, H Bratus, A Kolling, C Armaka, M Filer, A Michel, BA Gay, RE Buckley, CD Kollias, G Gay, S Ospelt, C |
| author_sort | Frank-Bertoncelj, M |
| collection | OXFORD |
| description | A number of human diseases, such as arthritis and atherosclerosis, include characteristic pathology in specific anatomical locations. Here we show transcriptomic differences in synovial fibroblasts from different joint locations and that HOX gene signatures reflect the joint-specific origins of mouse and human synovial fibroblasts and synovial tissues. Alongside DNA methylation and histone modifications, bromodomain and extra-terminal reader proteins regulate joint-specific HOX gene expression. Anatomical transcriptional diversity translates into joint-specific synovial fibroblast phenotypes with distinct adhesive, proliferative, chemotactic and matrix-degrading characteristics and differential responsiveness to TNF, creating a unique microenvironment in each joint. These findings indicate that local stroma might control positional disease patterns not only in arthritis but in any disease with a prominent stromal component. |
| first_indexed | 2024-03-07T06:18:14Z |
| format | Journal article |
| id | oxford-uuid:f1d21a22-32c8-4466-a3e4-c2e203a9e533 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T06:18:14Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:f1d21a22-32c8-4466-a3e4-c2e203a9e5332022-03-27T11:59:00ZEpigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functionsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f1d21a22-32c8-4466-a3e4-c2e203a9e533Symplectic Elements at OxfordNature Publishing Group2017Frank-Bertoncelj, MTrenkmann, MKlein, KKarouzakis, ERehrauer, HBratus, AKolling, CArmaka, MFiler, AMichel, BAGay, REBuckley, CDKollias, GGay, SOspelt, CA number of human diseases, such as arthritis and atherosclerosis, include characteristic pathology in specific anatomical locations. Here we show transcriptomic differences in synovial fibroblasts from different joint locations and that HOX gene signatures reflect the joint-specific origins of mouse and human synovial fibroblasts and synovial tissues. Alongside DNA methylation and histone modifications, bromodomain and extra-terminal reader proteins regulate joint-specific HOX gene expression. Anatomical transcriptional diversity translates into joint-specific synovial fibroblast phenotypes with distinct adhesive, proliferative, chemotactic and matrix-degrading characteristics and differential responsiveness to TNF, creating a unique microenvironment in each joint. These findings indicate that local stroma might control positional disease patterns not only in arthritis but in any disease with a prominent stromal component. |
| spellingShingle | Frank-Bertoncelj, M Trenkmann, M Klein, K Karouzakis, E Rehrauer, H Bratus, A Kolling, C Armaka, M Filer, A Michel, BA Gay, RE Buckley, CD Kollias, G Gay, S Ospelt, C Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions |
| title | Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions |
| title_full | Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions |
| title_fullStr | Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions |
| title_full_unstemmed | Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions |
| title_short | Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions |
| title_sort | epigenetically driven anatomical diversity of synovial fibroblasts guides joint specific fibroblast functions |
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