Single-cell RNA-seq of mouse androgenetic alopecia models treated with CXCL12-neutralizing antibody
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ABSTRACT:
PROVIDER: PRJNA1254628 | ENA |
REPOSITORIES: ENA
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Project description:Androgenetic alopecia (AGA) is a common form of hair loss characterized by follicular miniaturization, dermal fibrosis, and low-grade immune activation, yet the precise mediators linking androgen signaling to these tissue-level changes remain poorly defined. Here, we use single-cell RNA sequencing (scRNA-seq) to map the skin microenvironment in a testosterone-induced mouse model of AGA and assess the therapeutic impact of a CXCL12-neutralizing antibody. We find that androgen receptor-positive dermal fibroblasts are the principal source of CXCL12, which acts in an autocrine manner via ACKR3 to drive TGF-β–mediated extracellular matrix deposition. In parallel, CXCL12 signals through CXCR4 to reprogram a Sox2+ Twist1+ dermal papilla cell population toward a fibrotic, low-inductive state and expand a pro-fibrotic Trem2+ macrophage subset. Blockade of CXCL12 reverses these transcriptional and cellular alterations across stromal, follicular, and immune compartments, restoring a regenerative skin niche and supporting hair regrowth. These findings position CXCL12 as a central mediator of fibroimmune remodeling in AGA and establish its neutralization as a promising therapeutic strategy.
2025-06-01 | GSE295410 | GEO
Project description:It has been demonstrated that CXCL12 inhibits hair growth via CXCR4, and its neutralizing antibody (Ab) increases hair growth in alopecia areata (AA). However, the molecular mechanisms have not been fully elucidated. In the present study, we further prepared humanized CXCL12 Ab for AA treatment and investigated underlying molecular mechanisms using single-cell RNA sequencing. Subcutaneous injection of humanized CXCL12 Ab significantly delayed AA onset in mice, and dorsal skin was analyzed. T cells and dendritic cells/macrophages were increased in the AA model, but decreased after CXCL12 Ab treatment. Pseudobulk RNA sequencing identified 153 differentially expressed genes that were upregulated in AA model and downregulated after Ab treatment. Gene ontology analysis revealed that immune cell chemotaxis and cellular response to type II interferon were upregulated in AA model but downregulated after Ab treatment. We further identified key immune cell-related genes such as Ifng, Cd8a, Ccr5, Ccl4, Ccl5, and Il21r, which were colocalized with Cxcr4 in T cells and regulated by CXCL12 Ab treatment. Notably, CD8+ T cells were significantly increased and activated via Jak/Stat pathway in the AA model but inactivated after CXCL12 Ab treatment. Collectively, these results indicate that humanized CXCL12 Ab is promising for AA treatment via immune modulatory effects.
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Project description:Microbiome in the hair follicle of androgenetic alopecia patients
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Project description:To examined the genome-wide expression levels of lncRNAs in androgenetic alopecia tissues and paired adjacent normal tissues by microarray analysis. We identified numerous lncRNAs that were differentially regulated between androgenetic alopecia and paired normal tissues.
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Project description:Humanized CXCL12 Antibody Delays Onset and Modulates Immune Response in Alopecia Areata Mice
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Project description:Protein profiling offers an effective approach to characterizing the departure from normal of epidermis in disease states. The present investigation tested the hypothesis that the differentiation of epidermal corneocytes is perturbed in the forehead of subjects exhibiting frontal fibrosing alopecia. To this end, samples were collected by tape stripping from subjects diagnosed with this condition and compared to those from asymptomatic control subjects and from those exhibiting androgenetic alopecia. Unlike the latter, which exhibited only 3 proteins significantly different from controls, forehead samples from frontal fibrosing alopecia subjects displayed 72 proteins significantly different from controls, nearly two-thirds having lower expression. Comparison to corresponding profiles in scalp samples from frontal fibrosing alopecia and androgenetic alopecia suggested the perturbation of epidermal differentiation in the former was even greater in the scalp.
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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.
2023-08-30 | GSE212757 | GEO
Project description: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.
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Project description:Adipose transcriptome in the scalp of androgenetic alopecia
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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)
2012-03-26 | E-GEOD-36169 | biostudies-arrayexpress