Single cell analysis of the fibrotic landscape in Dupuytren's disease
<p>Fibrotic disorders represent some of the most devastating and poorly treated conditions in the Western World. Despite this, effective therapeutic interventions have yet to be identified for many of these conditions. A major barrier to identification of novel targets and successful clinical...
| 主要作者: | |
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| 其他作者: | |
| 格式: | Thesis |
| 語言: | English |
| 出版: |
2019
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| _version_ | 1826312179685523456 |
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| author | Layton, T |
| author2 | Nanchahal, J |
| author_facet | Nanchahal, J Layton, T |
| author_sort | Layton, T |
| collection | OXFORD |
| description | <p>Fibrotic disorders represent some of the most devastating and poorly treated conditions in the
Western World. Despite this, effective therapeutic interventions have yet to be identified for many
of these conditions. A major barrier to identification of novel targets and successful clinical
translation is a poor understanding of the myofibroblast-rich human fibrotic microenvironment,
compounded by the dynamic nature of this ecosystem. Here, I use Dupuytren’s disease (DD), a
localized fibrotic condition of the hand, as a model to construct a stromal cell atlas in human
fibrosis at single cell resolution. I identify three fibroblast subsets in DD, including a novel ICAM1<sup>+</sup>
chemokine-enriched fibroblast. After this, I demonstrate heterogeneity in myofibroblasts and
report discrete proliferative and CD82<sup>+</sup> populations. Using a newly optimized functional assay, I
show phenotypic diversity along modelled signature of myofibroblast activation and validate a
novel cell surface marker of this cell type, CD82, Finally, I show CD82 functions to regulate cell
cycle progression in DD myofibroblasts.</p> |
| first_indexed | 2024-03-07T08:23:38Z |
| format | Thesis |
| id | oxford-uuid:bc01f849-0af7-4ad9-9ca0-0cf07baa1aa8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:23:38Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | oxford-uuid:bc01f849-0af7-4ad9-9ca0-0cf07baa1aa82024-02-05T13:42:35ZSingle cell analysis of the fibrotic landscape in Dupuytren's diseaseThesishttp://purl.org/coar/resource_type/c_db06uuid:bc01f849-0af7-4ad9-9ca0-0cf07baa1aa8EnglishORA Deposit2019Layton, TNanchahal, JFurniss, D<p>Fibrotic disorders represent some of the most devastating and poorly treated conditions in the Western World. Despite this, effective therapeutic interventions have yet to be identified for many of these conditions. A major barrier to identification of novel targets and successful clinical translation is a poor understanding of the myofibroblast-rich human fibrotic microenvironment, compounded by the dynamic nature of this ecosystem. Here, I use Dupuytren’s disease (DD), a localized fibrotic condition of the hand, as a model to construct a stromal cell atlas in human fibrosis at single cell resolution. I identify three fibroblast subsets in DD, including a novel ICAM1<sup>+</sup> chemokine-enriched fibroblast. After this, I demonstrate heterogeneity in myofibroblasts and report discrete proliferative and CD82<sup>+</sup> populations. Using a newly optimized functional assay, I show phenotypic diversity along modelled signature of myofibroblast activation and validate a novel cell surface marker of this cell type, CD82, Finally, I show CD82 functions to regulate cell cycle progression in DD myofibroblasts.</p> |
| spellingShingle | Layton, T Single cell analysis of the fibrotic landscape in Dupuytren's disease |
| title | Single cell analysis of the fibrotic landscape in Dupuytren's disease |
| title_full | Single cell analysis of the fibrotic landscape in Dupuytren's disease |
| title_fullStr | Single cell analysis of the fibrotic landscape in Dupuytren's disease |
| title_full_unstemmed | Single cell analysis of the fibrotic landscape in Dupuytren's disease |
| title_short | Single cell analysis of the fibrotic landscape in Dupuytren's disease |
| title_sort | single cell analysis of the fibrotic landscape in dupuytren s disease |
| work_keys_str_mv | AT laytont singlecellanalysisofthefibroticlandscapeindupuytrensdisease |