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Colonic epithelial-derived FGF1 drives intestinal stem cell commitment toward goblet cells to suppress inflammatory bowel disease

Author

Listed:
  • Qian Lin

    (Wenzhou Medical University)

  • Sudan Zhang

    (Wenzhou Medical University)

  • Jiaren Zhang

    (Wenzhou Medical University)

  • Yi Jin

    (The First Affiliated Hospital of Wenzhou Medical University)

  • Taoli Chen

    (The Second Affiliated Hospital of Jiaxing University)

  • Ruoyu Lin

    (Wenzhou Medical University)

  • Jiaxuan Lv

    (Wenzhou Medical University)

  • Wenjing Xu

    (Wenzhou Medical University)

  • Tianzhen Wu

    (Wenzhou Medical University)

  • Shenyu Tian

    (Wenzhou Medical University)

  • Lei Ying

    (Wenzhou Medical University)

  • Xiaokun Li

    (Wenzhou Medical University)

  • Zhifeng Huang

    (Wenzhou Medical University
    The First Affiliated Hospital of Wenzhou Medical University)

  • Jianlou Niu

    (Wenzhou Medical University)

Abstract

Understanding the molecular mechanisms that regulate intestinal epithelial cell (IEC) renewal provides potential targets for inflammatory bowel disease (IBD). Growing evidence has highlighted the importance of epithelial signals in regulating intestinal stem cell (ISC) differentiation. However, it remains unclear which IEC-derived cytokines can precisely regulate ISC commitment toward specific mature cells. Here we systematically analyze all fibroblast growth factors (FGFs) expression and find that colonic FGF1 levels are inversely correlated with the severity of IBD in mouse models and patients. IEC-specific Fgf1 deletion leads to impaired goblet cell differentiation and exacerbated colitis, while pharmacological administration of recombinant FGF1 (rFGF1) alleviates colitis by enhancing goblet cell differentiation and improving colonic epithelial integrity. Mechanistic studies reveal that rFGF1 directs ISC differentiation toward goblet cells via FGFR2-TCF4-ATOH1 signaling axis. In conclusion, our study identifies an epithelial niche-derived FGF1 that regulates ISC commitment toward goblet cells, shedding light on strategies for treating IBD.

Suggested Citation

  • Qian Lin & Sudan Zhang & Jiaren Zhang & Yi Jin & Taoli Chen & Ruoyu Lin & Jiaxuan Lv & Wenjing Xu & Tianzhen Wu & Shenyu Tian & Lei Ying & Xiaokun Li & Zhifeng Huang & Jianlou Niu, 2025. "Colonic epithelial-derived FGF1 drives intestinal stem cell commitment toward goblet cells to suppress inflammatory bowel disease," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58644-2
    DOI: 10.1038/s41467-025-58644-2
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    References listed on IDEAS

    as
    1. Kaushal Parikh & Agne Antanaviciute & David Fawkner-Corbett & Marta Jagielowicz & Anna Aulicino & Christoffer Lagerholm & Simon Davis & James Kinchen & Hannah H. Chen & Nasullah Khalid Alham & Neil As, 2019. "Colonic epithelial cell diversity in health and inflammatory bowel disease," Nature, Nature, vol. 567(7746), pages 49-55, March.
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