{"doi":"10.1016/j.xfss.2024.07.008","title":"Engineered uterine primary myometrial cells with high-mobility group AT-hook 2 overexpression display a leiomyoma-like transcriptional and epigenomic phenotype","abstract":"OBJECTIVE: To determine if engineered high-mobility group AT-hook 2 (HMGA2) overexpressing uterine primary myometrial cells recapitulate the transcriptional and epigenomic features of HMGA2-subtype leiomyomas. DESIGN: Isolated primary, \"normal\" myometrial cells from three patients were engineered to overexpress HMGA2 to determine how HMGA2 establishes transcriptomic and epigenomic features of HMGA2-overexpressing leiomyoma. SETTING: Academic research laboratory. PATIENT(S): Primary myometrial cells were isolated from normal myometrium obtained from three patients undergoing hysterectomy. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Determined genome-wide transcriptomic and epigenomic features of engineered HMGA2-overexpressing uterine primary myometrial cells. RESULT(S): Engineered HMGA2-V5-overexpressing primary myometrial cells approximated the HMGA2 expression level observed in HMGA2-overexpression subtype leiomyoma. High-mobility group AT-hook 2-V5 expression resulted in differential expression of 1,612 genes (false discovery rate [FDR] < 0.05) that were found to be enriched in pathways associated with leiomyoma formation, including extracellular matrix organization. Comparative gene expression analysis between HMGA2-V5 engineered primary cells and HMGA2-overexpression subtype leiomyoma revealed significant overlap of differentially expressed genes. Mechanistically, HMGA2-V5 overexpression resulted in 41,323 regions with differential H3K27ac deposition (FDR < 0.05) and 205,605 regions of altered chromatin accessibility (FDR < 0.05). Transcription factor binding site analysis implicated the AP-1 family of transcription factors. CONCLUSION(S): High-mobility group AT-hook 2 overexpression induces leiomyoma-like transcriptomic and epigenomic modulations in myometrial cells.","journal":"F&S Science","year":2024,"id":475963,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9576,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1313246,"name":"Austin G. Holmes","orcid":"0000-0002-3578-2474","position":1,"is_corresponding":false},{"id":353302,"name":"Jian‐Jun Wei","orcid":"0000-0003-0281-2793","position":2,"is_corresponding":false},{"id":348047,"name":"J. Brandon Parker","orcid":"0000-0002-9152-8913","position":3,"is_corresponding":false},{"id":348048,"name":"Debabrata Chakravarti","orcid":"0000-0001-8446-8599","position":4,"is_corresponding":false},{"id":710543,"name":"Priyanka Saini","orcid":"0000-0002-7256-7001","position":0,"is_corresponding":true}],"reference_count":94,"raw_metadata":null,"created_at":"2026-07-19T02:06:25.428435Z","pmid":"39074663","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}