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Spatial transcriptome reveals disturbance of peri-infundibular immune infiltration in androgenetic alopecia

ABSTRACT: Several studies have suggested that in addition to androgen-sensitive dermal papilla cells, peri-infundibular immune infiltration is associated with the balding process in androgenetic alopecia (AGA). Nevertheless, investigations into the molecular signatures of this compartments are limited because none of the current techniques enable high-throughput profiling of specific pathological areas.

ORGANISM(S): Homo sapiens

PROVIDER: GSE240637 | GEO | 2023/08/11

REPOSITORIES: GEO

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RNA-seq of 3D-culture balding and non-balding dermal papilla cells

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. With the aim of elucidating genes involved in AGA pathogenesis, we cultured immortalised balding human dermal papilla cells (BAB) and immortalised non-balding human dermal papilla cells (BAN) in 3-dimensional culture format, and compared gene expression using RNA-seq between BAB and BAN cells.

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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)

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Spatial transcriptome reveals disturbance of peri-infundibular immune infiltration in androgenetic alopecia

Project description:Spatial transcriptome reveals disturbance of peri-infundibular immune infiltration in androgenetic alopecia

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Dermal papilla signature gene expression in immortalized human dermal papilla cells from balding and non-balding scalp

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Project description:To fully interrogate location-specific variations of the hair follicle in AGA and normal persons, we sought to perform a thorough and comprehensive transcripotome profiling of different locations of hair follicles (bulb portions, bulge portions) in balding and non-balding areas of AGA, with normal comparisons.

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Project description:Background: The male androgenetic alopecia (AGA) is the most common form of hair loss in men and is hereditary in more than 80% of cases and characterized by a distinct pattern of progressive hair loss starting from the frontal area and the vertex of the scalp. Although several genetic risk loci have been identified, relevant genes for AGA remain to be identified. Objectives: Herein, molecular biomarkers associated with premature AGA were identified through gene expression analysis using cDNA generated from scalp skin vertex biopsies of hairless/bold men with premature AGA and healthy volunteers. Results: This monocentric study reveals that genes encoding mast cell granule enzymes, inflammatory and immunoglobulin-associated immune mediators were significantly over-expressed in AGA. In contrast, under-expressed genes appear to be associated with the Wnt/β-catenin and BMP/TGF-β signaling pathways. Although the involvement of these pathways in hair follicle regeneration is well-described, functional interpretation of the transcriptomic data highlights different events that account for their inhibition. In particular, one of these events depends on the dysregulated expression of proopiomelanocortin (POMC), as confirmed by RT-qPCR and immunohistochemistry. In addition, a lower expression of CYP27B1 in AGA patients supports that alteration of vitamin D metabolism contributes to hair loss. Conclusion: Altogether, this study provides evidence for distinct molecular events contributing to alopecia that might be targeted for new therapeutic approaches.

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Transcriptome analysis reveals differences in vasculature signalling between human dermal papilla cells from balding and non-balding scalp

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2016-04-20 | GSE66664 | GEO

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