2. Academic Validation
  3. Fibroblast bioelectric signaling drives hair growth

Fibroblast bioelectric signaling drives hair growth

  • Cell. 2025 Aug 14:S0092-8674(25)00857-8. doi: 10.1016/j.cell.2025.07.035.
Daoming Chen 1,  Zhou Yu 2,  Wenbo Wu 1,  Yingxue Du 1,  Qianqian Du 1,  Huanwei Huang 1,  Yaqi Li 1,  Ting Xuan 1,  Ya-Chen Liang 2,  Yang Liu 3,  Zijuan Wang 4,  Rina Su 5,  Yi Zhao 6,  Qi Li 1,  Minmin Luo 3,  Fengchao Wang 1,  Ji Li 7,  Cheng-Ming Chuong 2,  Zhimiao Lin 8,  Ting Chen 9
Affiliations

Affiliations

  • 1 National Institute of Biological Sciences, Beijing, China.
  • 2 Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • 3 Chinese Institute for Brain Research, Beijing, China.
  • 4 Department of Dermatology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • 5 Department of Dermatology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
  • 6 Department of Dermatology, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China.
  • 7 Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
  • 8 Dermatology Hospital, Southern Medical University, Guangzhou, China. Electronic address: zhimiaolin@bjmu.edu.cn.
  • 9 National Institute of Biological Sciences, Beijing, China; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China. Electronic address: chenting@nibs.ac.cn.
PMID: 40818454 DOI: 10.1016/j.cell.2025.07.035
Abstract

Hair loss affects millions globally, significantly impacting quality of life and psychological well-being. Despite its prevalence, effective strategies for promoting human hair growth remain elusive. By investigating congenital generalized hypertrichosis terminalis (CGHT), a rare genetic disorder characterized by excessive hair growth, we discover that chromatin deletions or an inverted duplication disrupt the topologically associating domain (TAD), leading to the upregulation of the Potassium Channel KCNJ2 in dermal fibroblasts. Mouse genetics demonstrate that KCNJ2-mediated membrane hyperpolarization in dermal fibroblasts promotes hair growth by enhancing fibroblasts Wnt signaling responses, involving a reduction in intracellular calcium levels. Notably, fibroblast membrane potential oscillates during the normal hair cycle, with hyperpolarization specifically associated with the growth phase. Inducing fibroblast membrane depolarization delays the growth phase, while KCNJ2-mediated hyperpolarization rescues hair loss in aging and androgenetic alopecia models. These results uncover a previously unrecognized role of fibroblast bioelectricity in tissue regeneration, offering novel therapeutic avenues for hair loss treatment.

Keywords

KCNJ2; bioelectric signaling; fibroblast niche; hair follicle regeneration.

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