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GEO help: Mouse over screen elements for information. |
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| Status |
Public on May 31, 2021 |
| Title |
Single cell sequencing identifies serine proteases as regulators of myofibroblast differentiation |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Despite recent advances in understanding skin scarring, mechanisms triggering hypertrophic scar formation are still poorly understood. In the present study we performed single-cell sequencing of mature human hypertrophic scars and developing scars in mice. Compared to normal skin, we found significant differences in gene expression in most cell types present in scar tissue. Fibroblasts (FBs) showed the most prominent alterations in gene expression, displaying a distinct fibrotic signature. By comparing genes upregulated in murine FBs during scar development with genes highly expressed in mature human hypertrophic scars, we identified a group of serine proteases, tentatively involved in scar formation. Two of them, dipeptidyl-peptidase 4 (DPP4) and urokinase (PLAU), were further analyzed in functional assays, revealing a role in TGFβ1-mediated myofibroblast differentiation and over-production of components of the extracellular matrix (ECM) without interfering with the canonical TGFβ1 -signaling pathway. In this study, we delineate the genetic landscape of hypertrophic scars and present new insights into mechanisms involved in hypertrophic scar formation. Our data suggest the use of serine protease inhibitors for the treatment of skin fibrosis.
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| Overall design |
Single-cell transcriptome of human hypertrophic scars and human skin, and 6 and 8 weeks old mouse scars
>>> Raw data are unvailable due to patient privacy concerns <<<
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| Contributor(s) |
Vorstandlechner V, Laggner M, Copic D, Chen Y, Golabi B, Haslik W, Radtke C, Tschachler E, Ankersmit HJ, Mildner M |
| Citation(s) |
34716325, 37111549 |
| Submission date |
Aug 17, 2020 |
| Last update date |
May 12, 2023 |
| Contact name |
Vera Vorstandlechner |
| E-mail(s) |
vera.vorstandlechner@meduniwien.ac.at
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| Organization name |
Medical University of Vienna
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| Street address |
Waehringer Guertel 18-20
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| City |
Vienna |
| ZIP/Postal code |
1090 |
| Country |
Austria |
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| Platforms (2) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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| Samples (13)
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| Relations |
| BioProject |
PRJNA657534 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE156326_RAW.tar |
297.0 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
| Raw data not provided for this record |
| Processed data provided as supplementary file |
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