Project description:Research has shown that, apart from androgen-sensitive dermal papilla cells, hair follicle progenitor cell dynamics play a critical role in androgenetic alopecia (AGA). This study focuses on these progenitor cells, applying the spatial transcriptome technique to reveal molecular disturbances in the progenitor cells (CD34+ area) between AGA patients (PG-A) and normal controls (PG-C).
Project description:Testosterone is necessary for the development of male pattern baldness, known as androgenetic alopecia (AGA); yet the mechanisms for decreased hair growth in this disorder are unclear. Here, we show that prostaglandin D2 synthase (PTGDS) is elevated at the mRNA and protein levels in bald scalp compared to haired scalp of men with AGA. The product of PTGDS enzyme activity, prostaglandin D2 (PGD2), is similarly elevated in bald scalp. During normal follicle cycling in mice Ptgds and PGD2 levels increase immediately preceding the regression phase, suggesting an inhibitory effect on hair growth. We show that PGD2 inhibits hair growth in explanted human hair follicles and when applied topically to mice. Hair growth inhibition requires the PGD2 receptor G protein-coupled receptor 44 (GPR44), but not the prostaglandin D2 receptor 1(PTGDR). Furthermore, we find that a transgenic mouse, K14-Ptgs2, which targets prostaglandin-endoperoxide synthase 2 expression to the skin, demonstrates elevated levels of PGD2 in the skin and develops alopecia, follicular miniaturization and sebaceous gland hyperplasia, which are all hallmarks of human AGA. These results define PGD2 as an inhibitor of hair growth in AGA and suggest the PGD2-GPR44 pathway as a potential target for treatment. 5 individuals with Androgenetic Alopecia were biopsied at both their haired and bald scalp for mRNA purification and microarray (total 10 arrays)
Project description:Androgenetic alopecia (AGA, male patterned baldness) is a prevalent hair loss condition in males that develops due to the influence of androgens and genetic predisposition. The keratinocytes-surrounded spheroid dermal papilla (DP) at the base of the hair follicle is essential in hair morphogenesis and cycling. With the aim of elucidating genes involved in AGA pathogenesis, we co-cultured immortalised balding and non-balding human DP cells (DPC) derived from male AGA patients with epidermal keratinocyte (NHEK) using multi-interfacial polyelectrolyte complexation (MIPC) technique, and compared gene expression using RNA-seq between isolated balding and non-balding DP aggregates.
Project description:The key pathophysiological changes in androgenetic alopecia (AGA) are limited to hair follicles (HFs) in frontal and vertex regions, except for the occipital region. To identify biological differences among HF subpopulations. Paired vertex and occipital HFs from 10 male AGA donors were collected for RNA-seq assay. Furthermore, hair follicle and cell experiments were conducted on the identified key genes to reveal their roles in AGA. Our study aimed to uncover potential lncRNA indicators for AGA and reveal the potential mechanism underlying the involvement of AL136131.3 in hair growth in AGA.
Project description:Scarring alopecia consists of a collection of disorders characterized by destruction of hair follicles, replacement with fibrous scar tissue, and irreversible hair loss. Alopecia affects men and women worldwide and can be a significant source of psychological stress and depression for affected individuals. The purpose of this study was to explore metabolic profiles in scalp tissue samples from normal control subjects (n=6) and in matched samples obtained from affected (n=12) and unaffected (n=12) areas of the scalp in patients with lymphocytic Frontal Fibrosing Alopecia (FFA). Frontal fibrosing alopecia results from destruction of hair follicles by an inflammatory lymphocytic infiltrate that is localized around the upper portion of the hair follicle.
Project description:Mouse back skin was disassociated to single cells, sorted by cell surface markers and tested by microarrray To compare the gene expression of mouse bulge (CD34+CD200+CD49+) versus secondary hair germ (CD34-CD200+CD49+) versus interfollicular epidermis (CD34-CD200-CD49+) xx Bald scalp retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells 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. 4 independent biologic replicates (each pooled from 3 distinct mice) were sorted for Mouse bulge (CD34+CD200+CD49+) versus secondary hair germ (CD34-CD200+CD49+) versus interfollicular epidermis (CD34-CD200-CD49+)
Project description:To identify differentially expressed genes in androgenetic alopecia specifically in the adipose, adipose tissue samples from affected male participants were collected through punch biopsy at two different sites: bald (frontal) and normal (occipital,as control) scalp. After removal of the epidermis, dermis and hair follicle, we isolated RNA from the remaining adipose layer of the bald and normal scalp then performed gene expression analysis on the RNA-seq data to compare the profiles of the bald and normal scalp.
Project description:Autoimmune alopecia is a prevalent, highly morbid disease. The inflammatory pathways causing hair loss are not well characterized. We profiled two tissue microarrays comparing healthy skin to scarring alopecia and alopecia areata via spatial transcriptomics to analyze the genes and pathways dysregulated in autoimmune alopecia in direct proximity to the hair follicle.