Abstract：
OBJECTIVE: To study the possible role for HMGA2 overexpression in differentiated myometrial cells and its potential to induce a stem cell-like or dedifferentiating phenotype and drive fibroid development.
METHODS: Myometrial cells were immortalized and transduced with an HMGA2 lentivirus to produce HMGA2hi cells. In vitro stem cell assays were conducted, and ribonucleic acid from HMGA2hi and control cells as well as fibroid-free myometrial and HMGA2 fibroid (HMGA2F) tissues were submitted for ribonucleic acid sequencing.
METHODS: University research laboratory.
METHODS: Women who underwent hysterectomy for symptomatic uterine fibroids or other gynecological conditions.
METHODS: Not applicable.
METHODS: In vitro stem cell-like properties from myometrial cell lines. Ribonucleic acid sequencing and collagen production of HMGA2-overexpressing primary leiomyoma tissue and cell lines.
RESULTS: HMGA2hi cells had enhanced self-renewal capacity, decreased proliferation, and a greater ability to differentiate into other mesenchymal cell types. HMGA2hi cells exhibited a stem cell-like signature and shared transcriptomic similarities with HMGA2F. Moreover, dysregulated extracellular matrix pathways were observed in both HMGA2hi cells and HMGA2F.
CONCLUSIONS: Our findings show that HMGA2 overexpression may drive myometrial cells to dedifferentiate into a more plastic phenotype and provide evidence for an alternative mechanism for fibroid etiology, suggesting that fibroids arise not only from a mutated stem cell but also from a mutated differentiated myometrial cell.
METHODS: Myometrial cells were immortalized and transduced with an HMGA2 lentivirus to produce HMGA2hi cells. In vitro stem cell assays were conducted, and ribonucleic acid from HMGA2hi and control cells as well as fibroid-free myometrial and HMGA2 fibroid (HMGA2F) tissues were submitted for ribonucleic acid sequencing.
METHODS: University research laboratory.
METHODS: Women who underwent hysterectomy for symptomatic uterine fibroids or other gynecological conditions.
METHODS: Not applicable.
METHODS: In vitro stem cell-like properties from myometrial cell lines. Ribonucleic acid sequencing and collagen production of HMGA2-overexpressing primary leiomyoma tissue and cell lines.
RESULTS: HMGA2hi cells had enhanced self-renewal capacity, decreased proliferation, and a greater ability to differentiate into other mesenchymal cell types. HMGA2hi cells exhibited a stem cell-like signature and shared transcriptomic similarities with HMGA2F. Moreover, dysregulated extracellular matrix pathways were observed in both HMGA2hi cells and HMGA2F.
CONCLUSIONS: Our findings show that HMGA2 overexpression may drive myometrial cells to dedifferentiate into a more plastic phenotype and provide evidence for an alternative mechanism for fibroid etiology, suggesting that fibroids arise not only from a mutated stem cell but also from a mutated differentiated myometrial cell.
摘要：
目的：研究HMGA2过表达在分化的子宫肌层细胞中的可能作用及其诱导干细胞样或去分化表型和驱动肌瘤发展的潜力。
方法:使子宫肌层细胞永生化并用HMGA2慢病毒转导以产生HMGA2hi细胞。进行体外干细胞测定，并将来自HMGA2hi和对照细胞的RNA以及无纤维瘤子宫肌层（MyoN）和HMGA2纤维瘤（HMGA2F）组织进行RNA测序。
方法：大学研究实验室研究对象：因有症状的子宫肌瘤或其他妇科疾病而接受子宫切除术的妇女。
方法：不适用。
方法：来自子宫肌层细胞系的体外干细胞样特性。过表达HMGA2的原发性平滑肌瘤组织和细胞系的RNA测序和胶原蛋白产生。
结果：HMGA2hi细胞具有增强的自我更新能力，减少增殖，并且具有更大的分化为其他间充质细胞类型的能力。HMGA2hi细胞表现出干细胞样特征，并与HMGA2F具有转录组相似性。此外，在HMGA2hi细胞和HMGA2F中均观察到失调的细胞外基质途径。
结论：我们的研究结果表明，HMGA2过表达促使子宫肌层细胞去分化为更可塑性的表型，并为纤维化病因的替代机制提供了证据。这表明子宫肌瘤不仅可能来自突变的干细胞，也可能来自突变的分化的子宫肌层细胞。
方法:使子宫肌层细胞永生化并用HMGA2慢病毒转导以产生HMGA2hi细胞。进行体外干细胞测定，并将来自HMGA2hi和对照细胞的RNA以及无纤维瘤子宫肌层（MyoN）和HMGA2纤维瘤（HMGA2F）组织进行RNA测序。
方法：大学研究实验室研究对象：因有症状的子宫肌瘤或其他妇科疾病而接受子宫切除术的妇女。
方法：不适用。
方法：来自子宫肌层细胞系的体外干细胞样特性。过表达HMGA2的原发性平滑肌瘤组织和细胞系的RNA测序和胶原蛋白产生。
结果：HMGA2hi细胞具有增强的自我更新能力，减少增殖，并且具有更大的分化为其他间充质细胞类型的能力。HMGA2hi细胞表现出干细胞样特征，并与HMGA2F具有转录组相似性。此外，在HMGA2hi细胞和HMGA2F中均观察到失调的细胞外基质途径。
结论：我们的研究结果表明，HMGA2过表达促使子宫肌层细胞去分化为更可塑性的表型，并为纤维化病因的替代机制提供了证据。这表明子宫肌瘤不仅可能来自突变的干细胞，也可能来自突变的分化的子宫肌层细胞。
