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| Status |
Public on Jul 31, 2024 |
| Title |
JAK-STAT1 as therapeutic target for EGFR deficiency-associated inflammation and scarring alopecia (scRNA-seq) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The hair follicle stem cell niche is an immune-privileged microenvironment, characterized by reduced antigen presentation, thus shielding against permanent immune-mediated tissue damage. In this study, we demonstrated the protective role of hair follicle-specific epidermal growth factor receptor (EGFR) against scarring hair follicle destruction. Mechanistically, disruption of EGFR signalling generated a cell-intrinsic hypersensitivity within the JAK-STAT1 pathway, which, synergistically with interferon gamma expressing CD8 T-cell and NK-cell-mediated inflammation, compromised the stem cell niche. Hair follicle-specific genetic depletion of either JAK1/2 or STAT1 or therapeutic inhibition of JAK1/2 ameliorated the inflammation, restored skin barrier function and activated the residual stem cells to resume hair growth in mouse models of epidermal and hair follicle-specific EGFR deletion. Skin biopsies from EGFR inhibitor-treated and cicatricial alopecia patients indicated active STAT1 signalling and interferon target expression. Notably, a case study of folliculitis decalvans, characterized by progressive hair loss, scaling and perifollicular erythema, demonstrated successful treatment with JAK1/2 inhibition. Our findings offer molecular insights and present a mechanism-based therapeutic strategy for addressing chronic folliculitis associated with EGFR-inhibitor anti-cancer therapy and cicatricial alopecia.
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| Overall design |
In order to expand the depth of the immunological analysis, we performed single-cell RNA sequencing of the hair follicle and immune cell compartment of 4 EGFRdeltaEgr2 mice at 3 months of age.
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| Contributor(s) |
Strobl K, Jin R, Bauer T |
| Citation missing |
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| Submission date |
Jul 31, 2024 |
| Last update date |
Aug 01, 2024 |
| Contact name |
Thomas Bauer |
| E-mail(s) |
thomas.bauer@meduniwien.ac.at
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| Organization name |
Medical University of Vienna
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| Department |
Center for Cancer Research
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| Lab |
Bauer Lab
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| Street address |
Borschkegasse 8A
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| City |
Vienna |
| State/province |
Vienna |
| ZIP/Postal code |
1090 |
| Country |
Austria |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (1) |
| GSM8432472 |
Epidermis, Egfr-floxed Egr2-Cre, 4 reps pooled, scRNA-seq |
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| Relations |
| BioProject |
PRJNA1142442 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE273572_RAW.tar |
109.5 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
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