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

Journal: nature communications

Authors:  Jihyeon Myeong^1,14, Minho Lee ^2,14, Bawool Lee^1,3,14, Joon Hyung Kim², Yeji Nam4, Yeseul Choi^5,6, Jeongmin Kim¹, Se Young Jeon^7,8, HaewonShim Da-Ryung Jung⁹, Youngjin Shin², Minsoo Jeong⁹,ByungmooOh^1,3, Jaehun Jung ²,ChristineS.Kim^1,3, Hyung Soo Han^5,6,8,10, Jae-HoShin⁹, Yoon Hee Lee^7,8,11, Nora Jee-Young Park^8,12,13, Gun Oh Chong ^7,8,11,*, Youngtae Jeong^1,3,*

Affiliations

 ¹ Department of New Biology, DGIST, Daegu, Korea

 ² Department of Life Science, Dongguk University, Gyeonggi-do, Korea

 ³ New Biology Research Center, DGIST,Daegu,Korea

 ⁴ School of UndergraduateStudies, DGIST,Daegu,Korea

 ⁵ GraduateProgram,DepartmentofBiomedicalScience,KyungpookNational University School of Medicine, Daegu, Korea

 ⁶ BK21 Four Program, Kyungpook National University School of Medicine, Daegu, Korea

 ⁷ Department of Obstetrics and Gynecology, Kyungpook National University Chilgok Hospital, Daegu, Korea

 ⁸ Clinical Omics Institute, Kyungpook National University, Daegu, Korea

 ⁹ Department of Applied Biosciences, Kyungpook National University, Daegu, Korea

 ¹⁰ Department of Physiology, Kyungpook National Uni versity School of Medicine, Daegu, Korea

 ¹¹ Department of Obstetrics and Gynecology, Kyungpook National University School of Medicine, Daegu, Korea

 ¹² DepartmentofPathology,KyungpookNationalUniversityChilgokHospital,Daegu,Korea

 ¹³ DepartmentofPathology,KyungpookNationalUniversitySchool of Medicine, Daegu, Korea

 ¹⁴ These authors contributed equally: Jihyeon Myeong, Minho Lee, Bawool Lee.

 ^* Correspondence

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.

DOI:  https://doi.org/10.1038/s41467-025-57323-6

​Published: 08 March 2025

붙임: Microbial metabolites control self-renewal and precancerous progression of human cervical stem cells.pdf