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Microbial metabolites control self-renewal and precancerous progression of human cervical stem cells
- Authors
- Myeong, Jihyeon; Lee, Minho; Lee, Bawool; Kim, Joon Hyung; Nam, Yeji; Choi, Yeseul; Kim, Jeongmin; Jeon, Se Young; Shim, Haewon; Jung, Da-Ryung; Shin, Youngjin; Jeong, Minsoo; Oh, Byungmoo; Jung, Jaehun; Kim, Christine S.; Han, Hyung Soo; Shin, Jae-Ho; Lee, Yoon Hee; Park, Nora Jee-Young; Chong, Gun Oh; Jeong, Youngtae
- Issue Date
- Mar-2025
- Publisher
- Nature Portfolio
- Keywords
- Hematoxylin; Lactic Acid; Phosphatidylinositol 3 Kinase; Cd24 Antigen; Lactic Acid; Phosphatidylinositol 3-kinases; Yap-signaling Proteins; Yap1 Protein, Human; Cell Surface Marker; Hematoxylin; Lactic Acid; Cd24 Antigen; Phosphatidylinositol 3 Kinase; Yap Signaling Protein; Yap1 Protein, Human; Growth Response; Human Activity; Metabolite; Microbial Activity; Public Health; Rna; Adult; Animal Experiment; Article; Carcinogenesis; Cell Differentiation; Controlled Study; Ectocervix; Female; Flow Cytometry; Human; Human Cell; Human Tissue; Immunohistochemistry; Lactobacillus; Metabolomics; Mouse; Neoplastic Cell Transformation; Nonhuman; Organoid; Rna Isolation; Rna Sequencing; Single Cell Rna Seq; Stem Cell Self-renewal; Uterine Cervix Cancer; Whole Exome Sequencing; Animal; Cancer Stem Cell; Cell Self-renewal; Cytology; Disease Exacerbation; Genetics; Metabolism; Microbiology; Pathology; Precancer; Single Cell Analysis; Stem Cell; Uterine Cervix; Uterine Cervix Tumor; Animals; Cd24 Antigen; Cell Self Renewal; Cervix Uteri; Disease Progression; Female; Humans; Lactic Acid; Mice; Neoplastic Stem Cells; Organoids; Phosphatidylinositol 3-kinases; Precancerous Conditions; Single-cell Analysis; Stem Cells; Uterine Cervical Neoplasms; Yap-signaling Proteins
- Citation
- Nature Communications, v.16, no.1, pp 1 - 21
- Pages
- 21
- Indexed
- SCIE
SCOPUS
- Journal Title
- Nature Communications
- Volume
- 16
- Number
- 1
- Start Page
- 1
- End Page
- 21
- ISSN
- 2041-1723
2041-1723
- 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. © The Author(s) 2025.
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Related Researcher
- Lee, Minho
- College of Life Science and Biotechnology (Department of Life Science)