Project description: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.
Project description: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.
Project description:RNA sequencing was performed on sorted populations of Lgr6-positive and Lgr6-negative keratinocytes from the interfollicular epidermis and the hair follicle/sebaceous gland, in order to determine the compartment-specific expression signatures of Lgr6+ progenitor cells.
Project description:In this study, in order to explore the role of autophagy of human hair follicle stem cells in hair growth, we explored new ideas for hair regrowth. In this study, rapamycin was used to treat hair follicle stem cells to promote autophagy, and the different expression of genes was observed by comparing with the blank control group.
Project description:Androgenetic alopecia (AGA) or common baldness results from a marked decrease in hair follicle size. This miniaturization may be related to loss of hair follicle stem or progenitor cells. To test this hypothesis, we analyzed bald and non-bald scalp from the same individuals for the presence of hair follicle stem and progenitor cells using flow cytometry to quantitate cells expressing CYTOKERATIN 15 (KRT15), CD200, CD34 and ALPHA-6-INTEGRIN (ITGA6). High levels of KRT15 expression correlated with stem cell properties of small cell size and quiescence. Cells with the highest level of KRT15 expression were maintained in bald scalp; however, distinct populations of CD200high ITGA6high cells and CD34-positive cells were markedly diminished. Consistent with a progenitor cell phenotype, the diminished populations localized closely to the stem-cell rich bulge area but were larger and more proliferative than the bulge stem cells. In functional assays, analogous CD200 high /Itga6 high cells from murine hair follicles were multipotent and generated new hair follicles in skin reconstitution assays. These findings suggest that a defect in stem cell activation plays a role in the pathogenesis of AGA. This SuperSeries is composed of the SubSeries listed below.
Project description:Mouse hair follicles undergo synchronized cycles. Cyclical regeneration and hair growth is fueled by hair follicle stem cells (HFSCs). We used ChIP-seq to unfold genome-wide chromatin landscapes of Nfatc1 and dissect the biological relevence of its upstream BMP signaling in HFSC aging. Telogen quiescent hair follicle stem cells (HFSCs) were FACS-purified for ChIP-sequcencing.
Project description:Mouse keratinocytes were isolated from K15-EGFP transgenic mice for FACS sorting. RNA samples from EGFP-high and alpha-6 integrin positive cells (hair follicle stem cells) and from EGFP negative and alpha-6 integrin positive cells were used for Microarray analysis. Keywords = stem cells Keywords = hair follicle Keywords = epidermis Keywords = alopecia Keywords: ordered