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Advances in transcriptomics, particularly single-cell RNA sequencing, have revolutionized uterine biological research by revealing the cellular heterogeneity and molecular mechanisms underlying disease states. Single-cell RNA sequencing and spatial transcriptomics have mapped endometrial and myometrial cellular landscapes, which helped to identify critical cell types, signaling pathways, and phase-specific dynamics. Said transcriptomic technologies also identified stromal and immune cell dysfunctions, such as fibroblast-to-myofibroblast transitions and impaired macrophage activity, which drive fibrosis, chronic inflammation, and lesion persistence in endometriosis. For endometrial cancer, scRNA-seq uncovered tumor microenvironmental complexities, identifying cancer-associated fibroblast subtypes and immune cell profiles contributing to progression and therapeutic resistance. Similarly, studies on adenomyosis highlighted disrupted signaling pathways, including Wnt and VEGF, and novel progenitor cell populations linked to tissue invasion and neuroinflammation, while single-cell approaches characterized smooth muscle and fibroblast subpopulations in uterine fibroids, elucidating their roles in extracellular matrix remodeling and signaling pathways like ERK and mTOR. Despite challenges such as scalability and reproducibility, single-cell transcriptomic approaches may have potential applications in biomarker discovery, therapeutic target identification, and personalized medicine in gynecological disorders.<\/jats:p>","DOI":"10.3390\/cells14030156","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T11:47:32Z","timestamp":1737460052000},"page":"156","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Mapping Human Uterine Disorders Through Single-Cell Transcriptomics"],"prefix":"10.3390","volume":"14","author":[{"given":"Sandra","family":"Boldu-Fern\u00e1ndez","sequence":"first","affiliation":[{"name":"Carlos Sim\u00f3n Foundation, INCLIVA Health Research Institute, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Lliberos","sequence":"additional","affiliation":[{"name":"Carlos Sim\u00f3n Foundation, INCLIVA Health Research Institute, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0902-9531","authenticated-orcid":false,"given":"Carlos","family":"Simon","sequence":"additional","affiliation":[{"name":"Carlos Sim\u00f3n Foundation, INCLIVA Health Research Institute, 46010 Valencia, Spain"},{"name":"Department of Obstetrics and Gynecology, Universidad de Valencia, 46010 Valencia, Spain"},{"name":"Department of Pediatrics, Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5866-6732","authenticated-orcid":false,"given":"Aymara","family":"Mas","sequence":"additional","affiliation":[{"name":"Carlos Sim\u00f3n Foundation, INCLIVA Health Research Institute, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/humupd\/dmaa036","article-title":"The Development of the Human Uterus: Morphogenesis to Menarche","volume":"27","author":"Habiba","year":"2021","journal-title":"Hum. 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