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诱导多能干细胞在探索多囊卵巢综合征(PCOS)病理生理学中的可能应用。

Induced Pluripotent Stem Cells as a Possible Approach for Exploring the Pathophysiology of Polycystic Ovary Syndrome (PCOS).

机构信息

Department of Obstetrics and Gynecology, University of Helsinki, Helsinki University Central Hospital, Haartmaninkatu 8, Helsinki, 00029 HUS, Finland.

Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.

出版信息

Stem Cell Rev Rep. 2024 Jan;20(1):67-87. doi: 10.1007/s12015-023-10627-w. Epub 2023 Sep 28.

Abstract

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine condition among women with pleiotropic sequelae possessing reproductive, metabolic, and psychological characteristics. Although the exact origin of PCOS is elusive, it is known to be a complex multigenic disorder with a genetic, epigenetic, and environmental background. However, the pathogenesis of PCOS, and the role of genetic variants in increasing the risk of the condition, are still unknown due to the lack of an appropriate study model. Since the debut of induced pluripotent stem cell (iPSC) technology, the ability of reprogrammed somatic cells to self-renew and their potential for multidirectional differentiation have made them excellent tools to study different disease mechanisms. Recently, researchers have succeeded in establishing human in vitro PCOS disease models utilizing iPSC lines from heterogeneous PCOS patient groups (iPSC). The current review sets out to summarize, for the first time, our current knowledge of the implications and challenges of iPSC technology in comprehending PCOS pathogenesis and tissue-specific disease mechanisms. Additionally, we suggest that the analysis of polygenic risk prediction based on genome-wide association studies (GWAS) could, theoretically, be utilized when creating iPSC lines as an additional research tool to identify women who are genetically susceptible to PCOS. Taken together, iPSC may provide a new paradigm for the exploration of PCOS tissue-specific disease mechanisms.

摘要

多囊卵巢综合征(PCOS)是女性中最常见的内分泌疾病,具有生殖、代谢和心理特征的多效后遗症。虽然 PCOS 的确切起源尚不清楚,但已知它是一种复杂的多基因疾病,具有遗传、表观遗传和环境背景。然而,由于缺乏适当的研究模型,PCOS 的发病机制以及遗传变异增加患病风险的作用仍然未知。自从诱导多能干细胞(iPSC)技术问世以来,重编程体细胞的自我更新能力及其向多方向分化的潜力使它们成为研究不同疾病机制的优秀工具。最近,研究人员成功地利用来自异质 PCOS 患者群体的 iPSC 系建立了人类体外 PCOS 疾病模型(iPSC)。本综述首次总结了我们目前对 iPSC 技术在理解 PCOS 发病机制和组织特异性疾病机制中的意义和挑战的认识。此外,我们还提出,基于全基因组关联研究(GWAS)的多基因风险预测分析可以在创建 iPSC 系时作为一种额外的研究工具,用于识别在遗传上易患 PCOS 的女性。总之,iPSC 可能为探索 PCOS 组织特异性疾病机制提供新的范例。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8368/10799779/c2f788e470ed/12015_2023_10627_Fig1_HTML.jpg

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