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Integrated single-cell chromatin and transcriptomic analyses of human scalp reveal etiological insights into genetic risk for hair and skin disease [scRNA-Seq]

ABSTRACT: Integrated single-cell chromatin and transcriptomic analyses of human scalp reveal etiological insights into genetic risk for hair and skin disease [scRNA-Seq]

PROVIDER: PRJNA875446 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21377712.fastq.gz	Fastqsanger.gz
	SRR21377713.fastq.gz	Fastqsanger.gz
	SRR21377714.fastq.gz	Fastqsanger.gz
	SRR21377715.fastq.gz	Fastqsanger.gz
	SRR21377716.fastq.gz	Fastqsanger.gz

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Integrated single-cell chromatin and transcriptomic analyses of human scalp reveal etiological insights into genetic risk for hair and skin disease [scATAC-Seq]

Project description:In this study, we use single-cell ATAC sequencing (scATAC-seq) and single-cell RNA sequencing (scRNA-seq) to map chromatin accessibility and gene expression in human scalp samples from healthy patients and patients with alopecia areata

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Integrated single-cell chromatin and transcriptomic analyses of human scalp reveal etiological insights into genetic risk for hair and skin disease [scRNA-Seq]

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Integrated single-cell chromatin and transcriptomic analyses of human scalp reveal etiological insights into genetic risk for hair and skin disease

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Integrated single-cell chromatin and transcriptomic analyses of human scalp reveal etiological insights into genetic risk for hair and skin disease

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Prostaglandin D2 Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia

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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Bald scalp retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells

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.

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