{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T22:15:38Z","timestamp":1792880138978,"version":"4.5.0"},"reference-count":58,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2020,8,19]],"date-time":"2020-08-19T00:00:00Z","timestamp":1597795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 HD057877"],"award-info":[{"award-number":["P01 HD057877"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50 HD098580"],"award-info":[{"award-number":["P50 HD098580"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1S10OD011996-01"],"award-info":[{"award-number":["1S10OD011996-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P01 HD057877"],"award-info":[{"award-number":["P01 HD057877"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA060553"],"award-info":[{"award-number":["CA060553"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u2013like 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\u2013like 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\u2032-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.<\/jats:p>","DOI":"10.1210\/endocr\/bqaa143","type":"journal-article","created":{"date-parts":[[2020,8,19]],"date-time":"2020-08-19T02:17:10Z","timestamp":1597803430000},"source":"Crossref","is-referenced-by-count":21,"title":["Targeting DNA Methylation Depletes Uterine Leiomyoma Stem Cell\u2013enriched Population by Stimulating Their Differentiation"],"prefix":"10.1210","volume":"161","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4369-4589","authenticated-orcid":false,"given":"Shimeng","family":"Liu","sequence":"first","affiliation":[{"name":"Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Yin","sequence":"additional","affiliation":[{"name":"Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingting","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel J","family":"Dotts","sequence":"additional","affiliation":[{"name":"Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy A","family":"Kujawa","sequence":"additional","affiliation":[{"name":"Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S","family":"Coon V","sequence":"additional","affiliation":[{"name":"Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4616-3123","authenticated-orcid":false,"given":"Hong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Shilatifard","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0850-8637","authenticated-orcid":false,"given":"Serdar E","family":"Bulun","sequence":"additional","affiliation":[{"name":"Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,8,19]]},"reference":[{"issue":"1","key":"2021121718170089400_CIT0001","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1210\/er.2012-1043","article-title":"Progesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast 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Steril."},{"issue":"3","key":"2021121718170089400_CIT0005","doi-asserted-by":"crossref","first-page":"211.e1","DOI":"10.1016\/j.ajog.2011.12.002","article-title":"The estimated annual cost of uterine leiomyomata in the United States","volume":"206","author":"Cardozo","year":"2012","journal-title":"Am J Obstet Gynecol."},{"issue":"4","key":"2021121718170089400_CIT0006","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1177\/1933719111432867","article-title":"Medical treatment of uterine leiomyoma","volume":"19","author":"Sabry","year":"2012","journal-title":"Reprod Sci."},{"issue":"42","key":"2021121718170089400_CIT0007","doi-asserted-by":"crossref","first-page":"17053","DOI":"10.1073\/pnas.1313650110","article-title":"Paracrine activation of WNT\/beta-catenin pathway in uterine leiomyoma stem cells promotes tumor growth","volume":"110","author":"Ono","year":"2013","journal-title":"Proc Natl Acad Sci U S 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Meyer","year":"2015","journal-title":"Sci 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