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  3. Direct reprogramming of human fibroblasts into hair-inducing dermal papilla cell-like cells by a single small molecule

Direct reprogramming of human fibroblasts into hair-inducing dermal papilla cell-like cells by a single small molecule

  • Biochem Pharmacol. 2025 Mar:233:116744. doi: 10.1016/j.bcp.2025.116744.
Qinglan Zeng 1,  Yihe Ma 2,  Ruizhao Cai 3,  Xinxin Li 4,  Yilin Luo 1,  Binkai Zheng 1,  Gaofeng Wang 5,  Xuejuan Xu 6,  Xusheng Wang 7,  Zhongjie Liu 8
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen 518107, China.
  • 2 Department of Respiratory and Allergy, Third Affiliated Hospital of Shenzhen University, Shenzhen 518020, China; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
  • 3 Department of Breast Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510275, China.
  • 4 School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen 518107, China; Center for Child Care and Mental Health, Shenzhen Children's Hospital Affiliated to Shantou University Medical College, Shenzhen 518026, China.
  • 5 Department of Pastic and Aesthetic Surgery, Nanfang Hospital of Southern Medical University, Guangzhou 510515, China.
  • 6 Department of Endocrinology, The First People's Hospital of Foshan, Foshan 528000, China. Electronic address: snowcaressyou@163.com.
  • 7 School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen 518107, China. Electronic address: wangxsh27@mail.sysu.edu.cn.
  • 8 Department of Anesthesiology, Shenzhen Children's Hospital, Yitian Road 7019, Shenzhen 518000, China. Electronic address: 13580562690@163.com.
PMID: 39798934 DOI: 10.1016/j.bcp.2025.116744
Abstract

Dermal papilla cells (DPCs) are a crucial subset of mesenchymal cells in the skin responsible for regulating hair follicle development and growth, making them invaluable for cell-based therapies targeting hair loss. However, obtaining sufficient DPCs with potent hair-inducing abilities remains a persistent challenge. In this study, the Food and Drug Administration (FDA)-approved drug library was utilized to screen small molecules capable of reprogramming readily accessible human skin fibroblasts into functional DPCs. In the initial screening, five candidate small molecules were identified from a pool of 1,817 compounds, and the small molecule peficitinib was further identified by the further hair follicle regeneration experiments. Following peficitinib treatment, fibroblasts derived from primary human foreskin and scalp exhibited the capability to induce hair growth and possessed a molecular profile highly similar to that of primary DPCs. We refer to these cells as dermal papilla cell-like cells (DPC-LCs). Furthermore, transcriptome analysis showed that the wingless/integrated (Wnt) signaling pathway and the transforming growth factor β (TGF-β) signaling pathway, both of which play crucial roles in hair follicle morphogenesis, are upregulated and enriched in these DPC-LCs. These functional DPC-LCs offer a promising avenue for obtaining a plentiful supply of hair-inducing cells, thereby advancing the development of therapeutic strategies for hair loss treatment.

Keywords

Dermal papilla cell-like cell; Dermal papilla cells; Direct reprogramming; Human fibroblasts; Peficitinib; Small molecules.

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