HMGA2 overexpression induces plasticity in myometrial cells and a transcriptomic profile more similar to that of uterine fibroids

Emmanuel N. Paul Ph.D., Tyler J. Carpenter B.S., Laura A. Pavliscak B.S., Abigail Z. Bennett B.S., Maria Ariadna Ochoa-Bernal Ph.D., Asgerally T. Fazleabas Ph.D., Jose M. Teixeira Ph.D.
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引用次数: 0

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.

Design

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.

Setting

University research laboratory.

Patient(s)

Women who underwent hysterectomy for symptomatic uterine fibroids or other gynecological conditions.

Intervention(s)

Not applicable.

Main Outcome Measure(s)

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.

Result(s)

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.

Conclusion(s)

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.
HMGA2 的过表达可诱导子宫肌细胞的可塑性,其转录组特征与子宫肌瘤更为相似。
目的研究HMGA2在分化的子宫肌细胞中过表达的可能作用及其诱导干细胞样或去分化表型和驱动子宫肌瘤发育的潜力。进行体外干细胞测定,并将来自HMGA2hi和对照细胞以及无子宫肌瘤和HMGA2肌瘤(HMGA2F)组织的核糖核酸提交核糖核酸测序。结果)HMGA2hi细胞的自我更新能力增强,增殖能力下降,分化成其他间充质细胞类型的能力增强。HMGA2hi细胞表现出干细胞样特征,并与HMGA2F具有相似的转录组。结论:我们的研究结果表明,HMGA2过表达可促使子宫肌细胞向更具可塑性的表型进行再分化,并为子宫肌瘤的另一种病因机制提供了证据,表明子宫肌瘤不仅源于突变的干细胞,也源于突变的分化子宫肌细胞。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
F&S science
F&S science Endocrinology, Diabetes and Metabolism, Obstetrics, Gynecology and Women's Health, Urology
CiteScore
2.00
自引率
0.00%
发文量
0
审稿时长
51 days
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