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Peer-reviewedCC BY 4.0Advanced Science

Single‐Cell Profiling Reveals a Protective WNT5A‐ATF3‐FOSB Signaling Axis in Hair Follicle Stem Cells During Androgenetic Alopecia

  • Ruiyu Luo1
  • Ke Fang2
  • Changjiang Zhao1
  • Jiachao Xiong1
  • Yuan Zhu1
  • Mingyang Lu1
  • He Yan1
  • Zihan Li3
  • Baojin Wu4
  • Hua Jiang1
  • Yufei Li1,5
5 affiliations
  1. 1Department of Plastic Surgery Shanghai East Hospital School of Medicine Tongji University Shanghai China
  2. 2School of Medicine Tongji University Shanghai China
  3. 3St. Hugh's College University of Oxford Oxford UK
  4. 4Department of Plastic Surgery Huashan Hospital Fudan University Shanghai China
  5. 5Shanghai East Hospital Nanjing Medical University Shanghai China
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Abstract

Androgenetic alopecia (AGA) is a common form of hair loss with limited treatment options, driven by poorly understood molecular mechanisms. Using single‐cell RNA sequencing of human scalp follicles from balding and non‐balding regions, we constructed a high‐resolution molecular anatomy atlas of the hair follicle and its microenvironment. We identified significant silencing of Wingless‐related integration site 5A (WNT5A) signaling, which was widely known as the trigger of non‐canonical WNT signaling pathway, in hair follicle stem cells (HFSCs) from balding areas, leading to downregulation of the transcription factor ATF3 and its target FOSB. Therapeutically, functional validation showed that activating the WNT5A‐ATF3‐FOSB axis maintained HFSC competence in AGA murine models and significantly inhibited the progression of AGA. Our findings reveal a critical molecular axis in AGA pathogenesis, highlighting its potential as a therapeutic target for hair loss disorders.

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Cite

BibTeXRIS
BibTeX
@article{luo2026singlecell,
  title = {{Single‐Cell Profiling Reveals a Protective WNT5A‐ATF3‐FOSB Signaling Axis in Hair Follicle Stem Cells During Androgenetic Alopecia}},
  author = {Ruiyu Luo and Ke Fang and Changjiang Zhao and Jiachao Xiong and Yuan Zhu and Mingyang Lu and He Yan and Zihan Li and Baojin Wu and Hua Jiang and Yufei Li},
  journal = {Advanced Science},
  year = {2026},
  month = aug,
  doi = {10.1002/advs.77109},
  url = {https://doi.org/10.1002/advs.77109},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Single‐Cell Profiling Reveals a Protective WNT5A‐ATF3‐FOSB Signaling Axis in Hair Follicle Stem Cells During Androgenetic Alopecia
AU  - Ruiyu Luo
AU  - Ke Fang
AU  - Changjiang Zhao
AU  - Jiachao Xiong
AU  - Yuan Zhu
AU  - Mingyang Lu
AU  - He Yan
AU  - Zihan Li
AU  - Baojin Wu
AU  - Hua Jiang
AU  - Yufei Li
PY  - 2026
DA  - 2026/08/12
JO  - Advanced Science
DO  - 10.1002/advs.77109
UR  - https://doi.org/10.1002/advs.77109
AB  - Androgenetic alopecia (AGA) is a common form of hair loss with limited treatment options, driven by poorly understood molecular mechanisms. Using single‐cell RNA sequencing of human scalp follicles from balding and non‐balding regions, we constructed a high‐resolution molecular anatomy atlas of the hair follicle and its microenvironment. We identified significant silencing of Wingless‐related integration site 5A (WNT5A) signaling, which was widely known as the trigger of non‐canonical WNT signaling pathway, in hair follicle stem cells (HFSCs) from balding areas, leading to downregulation of the transcription factor ATF3 and its target FOSB. Therapeutically, functional validation showed that activating the WNT5A‐ATF3‐FOSB axis maintained HFSC competence in AGA murine models and significantly inhibited the progression of AGA. Our findings reveal a critical molecular axis in AGA pathogenesis, highlighting its potential as a therapeutic target for hair loss disorders.
SN  - 2198-3844
ER  -