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Microbial metabolites control self-renewal and precancerous progression of human cervical stem cells

Author

Listed:
  • Jihyeon Myeong

    (DGIST)

  • Minho Lee

    (Dongguk University)

  • Bawool Lee

    (DGIST
    DGIST)

  • Joon Hyung Kim

    (Dongguk University)

  • Yeji Nam

    (DGIST)

  • Yeseul Choi

    (Kyungpook National University School of Medicine
    Kyungpook National University School of Medicine)

  • Jeongmin Kim

    (DGIST)

  • Se Young Jeon

    (Kyungpook National University Chilgok Hospital
    Kyungpook National University)

  • Haewon Shim

    (Dongguk University)

  • Da-Ryung Jung

    (Kyungpook National University)

  • Youngjin Shin

    (Dongguk University)

  • Minsoo Jeong

    (Kyungpook National University)

  • Byungmoo Oh

    (DGIST
    DGIST)

  • Jaehun Jung

    (Dongguk University)

  • Christine S. Kim

    (DGIST
    DGIST)

  • Hyung Soo Han

    (Kyungpook National University School of Medicine
    Kyungpook National University School of Medicine
    Kyungpook National University
    Kyungpook National University School of Medicine)

  • Jae-Ho Shin

    (Kyungpook National University)

  • Yoon Hee Lee

    (Kyungpook National University Chilgok Hospital
    Kyungpook National University
    Kyungpook National University School of Medicine)

  • Nora Jee-Young Park

    (Kyungpook National University
    Kyungpook National University Chilgok Hospital
    Kyungpook National University School of Medicine)

  • Gun Oh Chong

    (Kyungpook National University Chilgok Hospital
    Kyungpook National University
    Kyungpook National University School of Medicine)

  • Youngtae Jeong

    (DGIST
    DGIST)

Abstract

Cervical cancer is the fourth most common female cancer, with the uterine ectocervix being the most commonly affected site. However, cervical stem cells, their differentiation, and their regulation remain poorly understood. Here, we report the isolation of a population enriched for human cervical stem cells and their regulatory mechanisms. Using single-cell RNA sequencing, we characterize the cellular heterogeneity of the human ectocervix and identify cluster-specific cell surface markers. By establishing normal and precancerous cervical organoids and an intralingual transplantation system, we show that ITGB4 and CD24 enable enrichment of human and murine ectocervical stem cells. We discover that Lactobacilli-derived lactic acid regulates cervical stem cells’ self-renewal and early tumorigenesis through the PI3K-AKT pathway and YAP1. Finally, we show that D-lactic acid suppresses growth of normal and precancerous organoids, while L-lactic acid does not. Our findings reveal roles of human cervical stem cells and microbial metabolites in cervical health and diseases.

Suggested Citation

  • Jihyeon Myeong & Minho Lee & Bawool Lee & Joon Hyung Kim & Yeji Nam & Yeseul Choi & Jeongmin Kim & Se Young Jeon & Haewon Shim & Da-Ryung Jung & Youngjin Shin & Minsoo Jeong & Byungmoo Oh & Jaehun Jun, 2025. "Microbial metabolites control self-renewal and precancerous progression of human cervical stem cells," Nature Communications, Nature, vol. 16(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57323-6
    DOI: 10.1038/s41467-025-57323-6
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