IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-58644-2.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-58644-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-58644-2?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Xingxing Ren & Qiuyuan Liu & Peirong Zhou & Tingyue Zhou & Decai Wang & Qiao Mei & Richard A. Flavell & Zhanju Liu & Mingsong Li & Wen Pan & Shu Zhu, 2024. "DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Jia Li & Alan J. Simmons & Caroline V. Hawkins & Sophie Chiron & Marisol A. Ramirez-Solano & Naila Tasneem & Harsimran Kaur & Yanwen Xu & Frank Revetta & Paige N. Vega & Shunxing Bao & Can Cui & Regin, 2024. "Identification and multimodal characterization of a specialized epithelial cell type associated with Crohn’s disease," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    3. Jiacheng Wu & Xiaoqing Xu & Jiaqi Duan & Yangyang Chai & Jiaying Song & Dongsheng Gong & Bingjing Wang & Ye Hu & Taotao Han & Yuanyuan Ding & Yin Liu & Jingnan Li & Xuetao Cao, 2024. "EFHD2 suppresses intestinal inflammation by blocking intestinal epithelial cell TNFR1 internalization and cell death," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Manqiang Lin & Kimberly Hartl & Julian Heuberger & Giulia Beccaceci & Hilmar Berger & Hao Li & Lichao Liu & Stefanie Müllerke & Thomas Conrad & Felix Heymann & Andrew Woehler & Frank Tacke & Nikolaus , 2023. "Establishment of gastrointestinal assembloids to study the interplay between epithelial crypts and their mesenchymal niche," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Ying Wang & Jing Han & Guang Yang & Shuhui Zheng & Gaoshi Zhou & Xinjuan Liu & Xiaocang Cao & Guang Li & Bowen Zhang & Zhuo Xie & Li Li & Mudan Zhang & Xiaoling Li & Minhu Chen & Shenghong Zhang, 2024. "Therapeutic potential of the secreted Kazal-type serine protease inhibitor SPINK4 in colitis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    6. María A. Duque-Correa & David Goulding & Faye H. Rodgers & J. Andrew Gillis & Claire Cormie & Kate A. Rawlinson & Allison J. Bancroft & Hayley M. Bennett & Magda E. Lotkowska & Adam J. Reid & Annelies, 2022. "Defining the early stages of intestinal colonisation by whipworms," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    7. Ziyu Liang & Courtney E. Wilson & Bochuan Teng & Sue C. Kinnamon & Emily R. Liman, 2023. "The proton channel OTOP1 is a sensor for the taste of ammonium chloride," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    8. Elvira Mennillo & Yang Joon Kim & Gyehyun Lee & Iulia Rusu & Ravi K. Patel & Leah C. Dorman & Emily Flynn & Stephanie Li & Jared L. Bain & Christopher Andersen & Arjun Rao & Stanley Tamaki & Jessica T, 2024. "Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    9. Yue Wang & Yanbo Yu & Lixiang Li & Mengqi Zheng & Jiawei Zhou & Haifan Gong & Bingcheng Feng & Xiao Wang & Xuanlin Meng & Yanyan Cui & Yanan Xia & Shuzheng Chu & Lin Lin & Huijun Chang & Ruchen Zhou &, 2023. "Bile acid-dependent transcription factors and chromatin accessibility determine regional heterogeneity of intestinal antimicrobial peptides," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    10. Alba Garrido-Trigo & Ana M. Corraliza & Marisol Veny & Isabella Dotti & Elisa Melón-Ardanaz & Aina Rill & Helena L. Crowell & Ángel Corbí & Victoria Gudiño & Miriam Esteller & Iris Álvarez-Teubel & Da, 2023. "Macrophage and neutrophil heterogeneity at single-cell spatial resolution in human inflammatory bowel disease," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58644-2. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.