Cellular census of human fibrosis defines functionally distinct stromal cell types and states
Fibrotic disorders are some of the most devastating and poorly treated conditions in developed nations, yet effective therapeutics are not identified for many of them. A major barrier for the identification of targets and successful clinical translation is a limited understanding of the human fibrot...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Nature Research
2020
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| _version_ | 1797084453021941760 |
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| author | Layton, TB Williams, L McCann, F Zhang, M Fritszche, M Colin-York, H Cabrita, M Ng, MTH Feldmann, M Samson, S Furniss, D Xie, W Nanchahal, J |
| author_facet | Layton, TB Williams, L McCann, F Zhang, M Fritszche, M Colin-York, H Cabrita, M Ng, MTH Feldmann, M Samson, S Furniss, D Xie, W Nanchahal, J |
| author_sort | Layton, TB |
| collection | OXFORD |
| description | Fibrotic disorders are some of the most devastating and poorly treated conditions in developed nations, yet effective therapeutics are not identified for many of them. A major barrier for the identification of targets and successful clinical translation is a limited understanding of the human fibrotic microenvironment. Here, we construct a stromal cell atlas of human fibrosis at single cell resolution from patients with Dupuytren’s disease, a localized fibrotic condition of the hand. A molecular taxonomy of the fibrotic milieu characterises functionally distinct stromal cell types and states, including a subset of immune regulatory ICAM1+ fibroblasts. In developing fibrosis, myofibroblasts exist along an activation continuum of phenotypically distinct populations. We also show that the tetraspanin CD82 regulates cell cycle progression and can be used as a cell surface marker of myofibroblasts. These findings have important implications for targeting core pathogenic drivers of human fibrosis. |
| first_indexed | 2024-03-07T01:55:27Z |
| format | Journal article |
| id | oxford-uuid:9b8ced6d-faa5-4d23-b432-80b3f6195e23 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:55:27Z |
| publishDate | 2020 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:9b8ced6d-faa5-4d23-b432-80b3f6195e232022-03-27T00:29:33ZCellular census of human fibrosis defines functionally distinct stromal cell types and statesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9b8ced6d-faa5-4d23-b432-80b3f6195e23EnglishSymplectic ElementsNature Research2020Layton, TBWilliams, LMcCann, FZhang, MFritszche, MColin-York, HCabrita, MNg, MTHFeldmann, MSamson, SFurniss, DXie, WNanchahal, JFibrotic disorders are some of the most devastating and poorly treated conditions in developed nations, yet effective therapeutics are not identified for many of them. A major barrier for the identification of targets and successful clinical translation is a limited understanding of the human fibrotic microenvironment. Here, we construct a stromal cell atlas of human fibrosis at single cell resolution from patients with Dupuytren’s disease, a localized fibrotic condition of the hand. A molecular taxonomy of the fibrotic milieu characterises functionally distinct stromal cell types and states, including a subset of immune regulatory ICAM1+ fibroblasts. In developing fibrosis, myofibroblasts exist along an activation continuum of phenotypically distinct populations. We also show that the tetraspanin CD82 regulates cell cycle progression and can be used as a cell surface marker of myofibroblasts. These findings have important implications for targeting core pathogenic drivers of human fibrosis. |
| spellingShingle | Layton, TB Williams, L McCann, F Zhang, M Fritszche, M Colin-York, H Cabrita, M Ng, MTH Feldmann, M Samson, S Furniss, D Xie, W Nanchahal, J Cellular census of human fibrosis defines functionally distinct stromal cell types and states |
| title | Cellular census of human fibrosis defines functionally distinct stromal cell types and states |
| title_full | Cellular census of human fibrosis defines functionally distinct stromal cell types and states |
| title_fullStr | Cellular census of human fibrosis defines functionally distinct stromal cell types and states |
| title_full_unstemmed | Cellular census of human fibrosis defines functionally distinct stromal cell types and states |
| title_short | Cellular census of human fibrosis defines functionally distinct stromal cell types and states |
| title_sort | cellular census of human fibrosis defines functionally distinct stromal cell types and states |
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