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

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 () and Jianlou Niu ()
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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
Jianlou Niu: Wenzhou Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-58644-2

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