An innovative in vitro system unveils IGF1R signaling regulating Merkel cell generation

  • Stem Cell Reports. 2025 Dec 26:102756. doi: 10.1016/j.stemcr.2025.102756.
Huipu Yuan  1 ,  Chen Rui  1 ,  Yajun Zhang  2 ,  Jun Liu  3 ,  Yanghui He  4 ,  Xia Wu  1 ,  Tuan Wang  5 ,  Zhengduo Zhang  6 ,  Chaochen Wang  7 ,  Ying Xiao  8
Affiliations
  • 1. Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
  • 2. Zhejiang University - University of Edinburgh Institute, International Campus, Haining, China.
  • 3. Dermatology Hospital of Southern Medical University, Guangzhou, China.
  • 4. School of Pharmacy, Jiangsu University, Zhenjiang, China.
  • 5. Hangzhou First People's Hospital Affiliated of Westlake University School of Medicine, Hangzhou, China.
  • 6. Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
  • 7. Zhejiang University - University of Edinburgh Institute, International Campus, Haining, China. Electronic address: [email protected].
  • 8. Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: [email protected].
PMID: 41455470 DOI: 10.1016/j.stemcr.2025.102756
Abstract

Merkel cells (MCs) are specialized mechanoreceptors crucial for tactile sensation, yet their developmental investigation remains challenging, particularly in humans, due to the lack of validated in vitro culture system. Here, we establish novel approaches, including short-term ex vivo vibrissae explants, innovative mouse skin organoids (mSKOs), and human pluripotent stem cell-derived skin organoids (hSKOs), to monitor MC development. We demonstrate that Polycomb repressive complex inhibitors (PRCis) efficiently promote MC generation in these culture systems. Through single-cell and spatial transcriptomics analysis, together with pharmacological screening, we identify IGF1R as a potential regulator of MC formation, which likely exerts its effects through the Akt pathway. Furthermore, we validate the role of FGFR2 signaling in MC generation. These systems constitute a versatile platform that harnesses complementary strengths to not only advance MC biology and skin development but also enable stem cell research, supporting organoid-based disease modeling, therapeutic compound screening, and regenerative medicine.

Keywords
IGF1R signaling; Merkel cell; skin organoid; tactile disorder; touch development.
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