Microbial metabolites control self-renewal and precancerous progression of human cervical stem cells
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 ce...
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Nature Portfolio
2025-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-57323-6 |
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| author | 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 Youngtae Jeong |
| author_facet | 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 Youngtae Jeong |
| author_sort | Jihyeon Myeong |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-08a598631fbc411ca7cae6a9b16442e9 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-08a598631fbc411ca7cae6a9b16442e92025-08-20T03:05:45ZengNature PortfolioNature Communications2041-17232025-03-0116112110.1038/s41467-025-57323-6Microbial metabolites control self-renewal and precancerous progression of human cervical stem cellsJihyeon Myeong0Minho Lee1Bawool Lee2Joon Hyung Kim3Yeji Nam4Yeseul Choi5Jeongmin Kim6Se Young Jeon7Haewon Shim8Da-Ryung Jung9Youngjin Shin10Minsoo Jeong11Byungmoo Oh12Jaehun Jung13Christine S. Kim14Hyung Soo Han15Jae-Ho Shin16Yoon Hee Lee17Nora Jee-Young Park18Gun Oh Chong19Youngtae Jeong20Department of New Biology, DGISTDepartment of Life Science, Dongguk UniversityDepartment of New Biology, DGISTDepartment of Life Science, Dongguk UniversitySchool of Undergraduate Studies, DGISTGraduate Program, Department of Biomedical Science, Kyungpook National University School of MedicineDepartment of New Biology, DGISTDepartment of Obstetrics and Gynecology, Kyungpook National University Chilgok HospitalDepartment of Life Science, Dongguk UniversityDepartment of Applied Biosciences, Kyungpook National UniversityDepartment of Life Science, Dongguk UniversityDepartment of Applied Biosciences, Kyungpook National UniversityDepartment of New Biology, DGISTDepartment of Life Science, Dongguk UniversityDepartment of New Biology, DGISTGraduate Program, Department of Biomedical Science, Kyungpook National University School of MedicineDepartment of Applied Biosciences, Kyungpook National UniversityDepartment of Obstetrics and Gynecology, Kyungpook National University Chilgok HospitalClinical Omics Institute, Kyungpook National UniversityDepartment of Obstetrics and Gynecology, Kyungpook National University Chilgok HospitalDepartment of New Biology, DGISTAbstract 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.https://doi.org/10.1038/s41467-025-57323-6 |
| spellingShingle | 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 Youngtae Jeong Microbial metabolites control self-renewal and precancerous progression of human cervical stem cells Nature Communications |
| title | Microbial metabolites control self-renewal and precancerous progression of human cervical stem cells |
| title_full | Microbial metabolites control self-renewal and precancerous progression of human cervical stem cells |
| title_fullStr | Microbial metabolites control self-renewal and precancerous progression of human cervical stem cells |
| title_full_unstemmed | Microbial metabolites control self-renewal and precancerous progression of human cervical stem cells |
| title_short | Microbial metabolites control self-renewal and precancerous progression of human cervical stem cells |
| title_sort | microbial metabolites control self renewal and precancerous progression of human cervical stem cells |
| url | https://doi.org/10.1038/s41467-025-57323-6 |
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