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| Status |
Public on Jun 03, 2024 |
| Title |
The impact of HPV8 on Lrig1+ and CD34+ hair follicle keratinocyte stem cell populations |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Despite epidermal turnover, the skin is host to a complex array of microbes including viruses, such as the human papillomavirus (HPV), which must infect and manipulate skin keratinocyte stem cells (KSC) to survive. This crosstalk between the virome and KSC populations remains largely unknown. Here, we investigated the effect of HPV8 on KSCs using various mouse models. We observed that the HPV8 early region gene E6 specifically caused Lrig1+hair follicle junctional zone KSC proliferation and expansion, which would facilitate viral transmission. Within Lrig1+KSCs specifically, HPV8 E6 bound intracellular p300 to phosphorylate the STAT3 transcriptional regulatory node. This induces a transcriptional switch from TAp63 to ΔNp63 expression, resulting in expansion of KSC into the overlying epidermis. HPV8 was associated with 70% of human actinic keratoses (AK). Together these results redefine human AK as an expansion of KSC, which lack protecting melanosomes and are thus susceptible to sun-light-induced malignant transformation.
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| Overall design |
To determine why HPV8 induced selective proliferation of the Lrig1+hair follicle junctional zone keratinocyte stem cells, but not other keratinocyte stem cells, we undertook a transcriptomic analysis of adjacent stem cell populations defined by Lrig1 and CD34 expression in adult mice. Both Lrig1+and CD34+flow-sorted keratinocytes were isolated from dorsal back skin of individual HPV8-CERtg and WT mice. We then performed gene expression profiling analysis on this RNA-seq data.
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| Web link |
http://10.1172/jci.insight.177898
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| Contributor(s) |
Patel GK, Gibbs A, Morgan HJ |
| Citation(s) |
38916963 |
| BioProject |
PRJNA1037145 |
| |
| Submission date |
Nov 13, 2023 |
| Last update date |
Sep 02, 2024 |
| Contact name |
Girish K Patel |
| E-mail(s) |
patelgk@cardiff.ac.uk
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| Organization name |
Cardiff University
|
| Street address |
Maindy Road
|
| City |
Cardiff |
| ZIP/Postal code |
CF244HQ |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE248056 |
The impact of HPV8 on hair follicle stem cell populations |
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