ArticleEndocrinology2020
Targeting DNA Methylation Depletes Uterine Leiomyoma Stem Cell-enriched Population by Stimulating Their Differentiation.
Article in Endocrinology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Therapeutic Potential of Solanum macrocarpon in Uterine Leiomyoma: In Vivo and In Silico Approaches.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- UTERINE FIBROIDS.Physiological reviews · 2025Review
- Review
- Review
- Epigallocatechin Gallate for the Treatment of Benign and Malignant Gynecological Diseases-Focus on Epigenetic Mechanisms.Nutrients · 2024Review
- A View on Uterine Leiomyoma Genesis through the Prism of Genetic, Epigenetic and Cellular Heterogeneity.International journal of molecular sciences · 2023Review
- H3K4me3 mediates uterine leiomyoma pathogenesis via neuronal processes, synapsis components, proliferation, and Wnt/β-catenin and TGF-β pathways.Reproductive biology and endocrinology : RB&E · 2023Review
- Epigenomic and enhancer dysregulation in uterine leiomyomas.Human reproduction update · 2022Review
- Article
- Review
- Epigenetic Regulation in Uterine Fibroids-The Role of Ten-Eleven Translocation Enzymes and Their Potential Therapeutic Application.International journal of molecular sciences · 2022Review
- PLP1 may serve as a potential diagnostic biomarker of uterine fibroids.Frontiers in genetics · 2022Article
- Uterine Fibroids: Hiding in Plain Sight.Physiology (Bethesda, Md.) · 2022Review
- Progesterone receptor-DNA methylation crosstalk regulates depletion of uterine leiomyoma stem cells: A potential therapeutic target.Stem cell reports · 2021Article
- Low variability in the underlying cellular landscape adversely affects the performance of interaction-based approaches for conducting cell-specific analyses of DNA methylation in bulk samples.Statistical applications in genetics and molecular biology · 2021Article
- Uterine Stem Cells and Benign Gynecological Disorders: Role in Pathobiology and Therapeutic Implications.Stem cell reviews and reports · 2021Review
- Towards an Epigenetic Treatment of Leiomyomas?Endocrinology · 2020Article
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10 authors at 2 institutions in 1 country.
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Abstract
Uterine leiomyoma (LM) is the most common tumor in women and can cause severe morbidity. Leiomyoma growth requires the maintenance and proliferation of a stem cell population. Dysregulated deoxyribonucleic acid (DNA) methylation has been reported in LM, but its role in LM stem cell regulation remains unclear. Here, we fluorescence-activated cell sorting (FACS)-sorted cells from human LM tissues into 3 populations: LM stem cell-like cells (LSC, 5%), LM intermediate cells (LIC, 7%), and differentiated LM cells (LDC, 88%), and we analyzed the transcriptome and epigenetic landscape of LM cells at different differentiation stages. Leiomyoma stem cell-like cells harbored a unique methylome, with 8862 differentially methylated regions compared to LIC and 9444 compared to LDC, most of which were hypermethylated. Consistent with global hypermethylation, transcript levels of TET1 and TET3 methylcytosine dioxygenases were lower in LSC. Integrative analyses revealed an inverse relationship between methylation and gene expression changes during LSC differentiation. In LSC, hypermethylation suppressed the genes important for myometrium- and LM-associated functions, including muscle contraction and hormone action, to maintain stemness. The hypomethylating drug, 5'-Aza, stimulated LSC differentiation, depleting the stem cell population and inhibiting tumor initiation. Our data suggest that DNA methylation maintains the pool of LSC, which is critical for the regeneration of LM tumors.
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