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

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 Jung, Christine S. Kim, Hyung Soo Han, Jae-Ho Shin, Yoon Hee Lee, Nora Jee-Young Park, Gun Oh Chong () and Youngtae Jeong ()
Additional contact information
Jihyeon Myeong: DGIST
Minho Lee: Dongguk University
Bawool Lee: DGIST
Joon Hyung Kim: Dongguk University
Yeji Nam: DGIST
Yeseul Choi: Kyungpook National University School of Medicine
Jeongmin Kim: DGIST
Se Young Jeon: Kyungpook National University Chilgok Hospital
Haewon Shim: Dongguk University
Da-Ryung Jung: Kyungpook National University
Youngjin Shin: Dongguk University
Minsoo Jeong: Kyungpook National University
Byungmoo Oh: DGIST
Jaehun Jung: Dongguk University
Christine S. Kim: DGIST
Hyung Soo Han: Kyungpook National University School of Medicine
Jae-Ho Shin: Kyungpook National University
Yoon Hee Lee: Kyungpook National University Chilgok Hospital
Nora Jee-Young Park: Kyungpook National University
Gun Oh Chong: Kyungpook National University Chilgok Hospital
Youngtae Jeong: DGIST

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-57323-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57323-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-57323-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().