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人羊膜间充质干细胞向产生孕激素/雄激素谱系的类固醇生成分化及向产生雌激素谱系的 WT1-KTS 分化。

Steroidogenic differentiation of human amniotic membrane-derived mesenchymal stem cells into a progesterone-/androgen-producing cell lineage by SF-1 and an estrogen-producing cell lineage by WT1-KTS.

机构信息

Department of Obstetrics and Gynecology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.

Department of Nursing, Faculty of Nursing and Welfare Sciences, Fukui Prefectural University, Fukui, Japan.

出版信息

Front Endocrinol (Lausanne). 2024 Sep 18;15:1410433. doi: 10.3389/fendo.2024.1410433. eCollection 2024.

Abstract

BACKGROUND

Sex steroid hormones, primarily synthesized by gonadal somatic cells, are pivotal for sexual development and reproduction. Mice studies have shown that two transcription factors, steroidogenic factor 1 (SF-1) and Wilms' tumor 1 (WT1), are involved in gonadal development. However, their role in human gonadal somatic differentiation remains unclear. We therefore aimed to investigate the roles of SF-1 and WT1 in human gonadal steroidogenic cell differentiation.

METHODS

Using a transient lentivirus-mediated gene expression system, we assessed the effects of SF-1 and WT1 expression on the steroidogenic potential of human amniotic membrane-derived mesenchymal stem cells (hAmMSCs).

RESULTS

SF-1 and WT1-KTS, a splice variant of WT1, played distinct roles in human steroidogenic differentiation of hAmMSCs. SF-1 induced hAmMSC differentiation into progesterone- and androgen-producing cell lineages, whereas WT1-KTS promoted hAmMSC differentiation into estrogen-producing cell lineages.

CONCLUSION

Our findings revealed that SF-1 and WT1-KTS play important roles in human gonadal steroidogenic cell differentiation, especially during ovarian development. These findings may pave the way for future studies on human ovarian differentiation and development.

摘要

背景

性类固醇激素主要由性腺体细胞合成,对性发育和生殖至关重要。小鼠研究表明,两种转录因子,即类固醇生成因子 1(SF-1)和维尔姆斯瘤 1(WT1),参与了性腺发育。然而,它们在人类性腺体细胞分化中的作用尚不清楚。因此,我们旨在研究 SF-1 和 WT1 在人类性腺甾体生成细胞分化中的作用。

方法

我们使用瞬时慢病毒介导的基因表达系统,评估了 SF-1 和 WT1 表达对人羊膜间充质干细胞(hAmMSCs)甾体生成潜能的影响。

结果

SF-1 和 WT1-KTS(WT1 的剪接变体)在 hAmMSC 的人类甾体生成分化中发挥了不同的作用。SF-1 诱导 hAmMSC 分化为孕激素和雄激素产生细胞谱系,而 WT1-KTS 则促进 hAmMSC 分化为雌激素产生细胞谱系。

结论

我们的发现表明 SF-1 和 WT1-KTS 在人类性腺甾体生成细胞分化中发挥重要作用,特别是在卵巢发育过程中。这些发现可能为未来的人类卵巢分化和发育研究铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5f1/11445051/496d149d561f/fendo-15-1410433-g001.jpg

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