{"title":"HMGA2过表达的工程子宫原代子宫肌细胞显示出类似子宫肌瘤的转录和表观基因组表型。","authors":"Priyanka Saini, Austin G Holmes, Jian-Jun Wei, J Brandon Parker, Debabrata Chakravarti","doi":"10.1016/j.xfss.2024.07.008","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Design: </strong>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.</p><p><strong>Setting: </strong>Academic research laboratory.</p><p><strong>Patient(s): </strong>Primary myometrial cells were isolated from normal myometrium obtained from three patients undergoing hysterectomy.</p><p><strong>Intervention(s): </strong>Not applicable.</p><p><strong>Main outcome measure(s): </strong>Determined genome-wide transcriptomic and epigenomic features of engineered HMGA2-overexpressing uterine primary myometrial cells.</p><p><strong>Result(s): </strong>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.</p><p><strong>Conclusion(s): </strong>High-mobility group AT-hook 2 overexpression induces leiomyoma-like transcriptomic and epigenomic modulations in myometrial cells.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Engineered uterine primary myometrial cells with high-mobility group AT-hook 2 overexpression display a leiomyoma-like transcriptional and epigenomic phenotype.\",\"authors\":\"Priyanka Saini, Austin G Holmes, Jian-Jun Wei, J Brandon Parker, Debabrata Chakravarti\",\"doi\":\"10.1016/j.xfss.2024.07.008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>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.</p><p><strong>Design: </strong>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.</p><p><strong>Setting: </strong>Academic research laboratory.</p><p><strong>Patient(s): </strong>Primary myometrial cells were isolated from normal myometrium obtained from three patients undergoing hysterectomy.</p><p><strong>Intervention(s): </strong>Not applicable.</p><p><strong>Main outcome measure(s): </strong>Determined genome-wide transcriptomic and epigenomic features of engineered HMGA2-overexpressing uterine primary myometrial cells.</p><p><strong>Result(s): </strong>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.</p><p><strong>Conclusion(s): </strong>High-mobility group AT-hook 2 overexpression induces leiomyoma-like transcriptomic and epigenomic modulations in myometrial cells.</p>\",\"PeriodicalId\":73012,\"journal\":{\"name\":\"F&S science\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-07-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"F&S science\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.xfss.2024.07.008\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"F&S science","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.xfss.2024.07.008","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Engineered uterine primary myometrial cells with high-mobility group AT-hook 2 overexpression display a leiomyoma-like transcriptional and epigenomic phenotype.
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.