Reproducibility of PD patient-specific midbrain organoid data for in vitro disease modeling

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-09-10 DOI:10.1016/j.isci.2025.113541

Elisa Zuccoli , Haya Al Sawaf , Mona Tuzza , Sarah L. Nickels , Alise Zagare , Jens C. Schwamborn

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Abstract

Midbrain organoids are advanced in vitro cellular models for disease modeling. They have been used successfully over the past decade for Parkinson’s disease (PD) research and drug development. The three-dimensional structure and multicellular composition allow disease research under more physiological conditions than is possible with conventional 2D cellular models. However, there are concerns in the field regarding the organoid batch-to-batch variability and thus the reproducibility of the results. In this manuscript, we generate multiple independent midbrain organoid batches derived from healthy individuals or glucocerebrosidase (GBA)-N370S mutation-carrying PD patients to evaluate the reproducibility of the GBA-N370S mutation-associated PD transcriptomic and metabolic signature as well as selected protein abundance. Our analysis shows that GBA-PD-associated phenotypes are reproducible across organoid generation batches and time points. This proves that midbrain organoids are not only suitable for PD in vitro modeling but also represent robust and highly reproducible cellular models.

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PD患者特异性中脑类器官数据在体外疾病建模中的可重复性

中脑类器官是一种先进的体外细胞模型，用于疾病建模。在过去的十年中，它们已经成功地用于帕金森氏症（PD）的研究和药物开发。与传统的二维细胞模型相比，三维结构和多细胞组成允许在更多生理条件下进行疾病研究。然而，在该领域存在关于类器官批次之间的可变性以及结果的可重复性的担忧。在本文中，我们从健康个体或携带葡萄糖脑苷酶(GBA)-N370S突变的PD患者中提取了多个独立的中脑类器官批次，以评估GBA-N370S突变相关PD转录组学和代谢特征的可重复性以及选定的蛋白质丰富度。我们的分析表明，gba - pd相关表型在类器官代批次和时间点上是可重复的。这证明了中脑类器官不仅适合PD体外建模，而且具有鲁棒性和高可重复性的细胞模型。

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

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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