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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: 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

ORGANISM(S): Homo sapiens

PROVIDER: GSE212447 | GEO | 2023/05/09

REPOSITORIES: GEO

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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

2023-05-09 | GSE212448 | GEO

First ruxolitinib treatment of human alopecia areata patients

Project description:Two patients with alopecia areata were treated with systemic ruxolitinib. Skin biopsies were taken before starting treatment and 12 weeks after starting treatment. We used microarrays to assess changes in gene expression of affected skin before and after starting treatment Two patients with alopecia areata were recruited for our study. Skin biopsies of affected scalp were taken prior to starting treatment with oral ruxolinitib. Additional skin biopsies were taken 12 weeks after starting treatment. Scalp skin biopsies were taken from patients without alopecia areata for comparison. RNA was extracted, cDNA libraries were made and profiled on affymetrix microarray chips.

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Human Alopecia Areata Skin Profiling

Project description:Our goal was to develop a transcriptomic description of affected alopecic scalp skin from patients with alopecia areata. 5 biological replicates of skin samples from 5 separate AA patients compared with 5 similar scalp samples from healthy control patients

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JAK3/TEC and TYK2/JAK1 inhibitors demonstrate significant improvement in scalp alopecia areata biomarkers

Project description:We present the biopsy sub-study results from the first randomized, placebo-controlled clinical trial in patients with alopecia areata (AA) with ≥50% scalp hair loss and ≤7 years since the last AA episode. In this sub-study, we evaluated the molecular responses to PF-06651600, an oral inhibitor of JAK3 and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family, and PF-06700841, an oral TYK2/JAK1 inhibitor, versus placebo in nonlesional and lesional scalp biopsies of biopsy samples from patients with AA.

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Project description:Our goal was to develop a transcriptomic description of affected alopecic scalp skin from patients with alopecia areata.

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Human Alopecia Areata Skin Biopsy Samples

Project description:Gene expression profiling of scalp skin biopsies from patients with alopecia areata or normal healthy controls Scalp skin punch biopsies were taken from the indicated patients and stored in PAXgene tissue containers for shipping to a central location, where the samples were processed

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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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Pilot open label clinical trial of oral ruxolitinib in patients with alopecia areata

Project description:This goal of these studies were to examine gene expression profiles of skin from patients with alopecia areata undergoing treatment with oral ruxoltinib. Microarray analysis was performed to assess changes in gene expression in affected scalp skin.

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Safety and Efficacy of the JAK Inhibitor Tofacitinib Citrate for Alopecia Areata and Variants

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Extensive alopecia areata is reversed by IL-23 cytokine antagonism

Project description:Alopecia areata (AA) is a prevalent disease associated with major emotional distress, and lacks effective, safe therapeutics for patients with extensive hair loss. This is the first report of hair regrowth with specific cytokine antagonism, in three patients with extensive hair loss ranging from 40% scalp involvement to alopecia universalis. Ustekinumab, an IL-12/23p40 antagonist that is highly effective in psoriasis, showed impressive ability to induce hair regrowth, coupled with suppression of inflammatory pathways and upregulation of hair keratins. Our report suggests that extensive AA is reversible using targeted treatments, opening the door for specific cytokine antagonism for this debilitating disease. We evaluated hair regrowth in three AA patients at 20 weeks after treatment with 3 subcutaneous doses of 90mg ustekinumab given at weeks 0, 4, and 16. Skin biopsies of lesional and non-lesional scalp (when available) were taken at baseline (week 0) and at week 20. We also obtained biopsies from three healthy individuals.

2015-12-08 | E-GEOD-74761 | biostudies-arrayexpress

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