Differential Expression between Human Dermal Papilla Cells from Balding and Non-Balding Scalps Reveals New Candidate Genes for Androgenetic Alopecia

Abstract

Androgenetic alopecia (AGA) is a common heritable and androgen-dependent hair loss condition in men. Twelve genetic risk loci are known to date, but it is unclear which genes at these loci are relevant for AGA. Dermal papilla cells (DPCs) located in the hair bulb are the main site of androgen activity in the hair follicle. Widely used monolayer-cultured primary DPCs in hair-related studies often lack dermal papilla characteristics. In contrast, immortalized DPCs have high resemblance to intact dermal papilla. We derived immortalized human DPC lines from balding (BAB) and non-balding (BAN) scalp. Both BAB and BAN retained high proportions of dermal papilla signature gene and versican protein expression. We performed expression analysis of BAB and BAN and annotated AGA risk loci with differentially expressed genes. We found evidence for AR but not EDA2R as the candidate gene at the AGA risk locus on chromosome X. Further, our data suggest TWIST1 (twist family basic helix-loop-helix transcription factor 1) and SSPN (sarcospan) to be the functionally relevant AGA genes at the 7p21.1 and 12p12.1 risk loci, respectively. Down-regulated genes in BAB compared to BAN were highly enriched for vasculature-related genes, suggesting that deficiency of DPC from balding scalps in fostering vascularization around the hair follicle may contribute to the development of AGA.

Androgenic Alopecia: Cross-Talk Between Cell Signal Transduction Pathways

“…Why do hair follicles have different sensitivity to androgens is still open question. There are few studies towards difference between androgen-dependent and androgen-independent hair follicles [8,[30][31][32][33][34][35].…”

“…Datasets with accession numbers GSE6664 [31] and GSE36169 [55] [65] could be uploaded from Gene Expression Omnibus (GEO) database [79]. Two more experiments were described by Midorikawa et al [34] and Kwack et al [48].…”

“…For example, two gene microarray analyses with DP cells from AGA frontal and occipital scalp areas reveal either high level of DKK1 expression in DP cells from bald frontal scalp [48] or diminished DKK1 expression [31]. Most probably, this mismatch is due to differences in methods for DP cells isolation and culture or different levels of DHT treatment between experiments.…”

“…GEO microarray dataset with accession number GSE66664 [31] compared gene expression in cultured immortalized human DP cells from balding (frontal) and nonbalding (occipital) scalps in response to DHT treatment. DP immortalized cell lines were obtained from two white 26-year-old men with Hamilton-Norwood grade IV AGA.…”

“…There is an important note that, among others, such genes as HEY1, SPRY1, PTGS1, EGR3 are considered to be DP signatures genes [31]. 2 and 1).…”