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Single-cell RNA-seq of mouse androgenetic alopecia models treated with CXCL12-neutralizing antibody

ABSTRACT: Single-cell RNA-seq of mouse androgenetic alopecia models treated with CXCL12-neutralizing antibody

PROVIDER: PRJNA1254628 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR33283947.fastq.gz	Fastqsanger.gz
	SRR33283948.fastq.gz	Fastqsanger.gz
	SRR33283949.fastq.gz	Fastqsanger.gz

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Single-cell RNA-seq of mouse androgenetic alopecia models treated with CXCL12-neutralizing antibody

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.

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Humanized CXCL12 Antibody Delays Onset and Modulates Immune Response in Alopecia Areata Mice

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Project description:Androgenetic alopecia (AGA) is characterized by progressive hair follicle miniaturization and remodeling of the skin microenvironment. To investigate cellular changes associated with AGA and the effects of DKK3 blockade, we performed single-cell RNA sequencing (scRNA-seq) of dorsal skin from a DHT-induced mouse model. Three experimental groups of male C3H/HeN mice were analyzed: vehicle control, DHT-treated AGA model, and DHT-treated mice receiving anti-DKK3 neutralizing antibody. Single-cell transcriptomic profiling identified cell population changes associated with DHT exposure and their modulation by anti-DKK3 treatment. This dataset provides a single-cell atlas of dorsal skin in the AGA model and following DKK3 inhibition.

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