Zagare Alise, Balaur Irina, Rougny Adrien, Saraiva Claudia, Gobin Matthieu, Monzel Anna S, Ghosh Soumyabrata, Satagopam Venkata P, Schwamborn Jens C
Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.
NPJ Parkinsons Dis. 2025 Mar 31;11(1):63. doi: 10.1038/s41531-025-00914-3.
Parkinson's disease (PD) is a progressive neurodegenerative disorder with no effective treatment. Advances in neuroscience and systems biomedicine now enable the use of complex patient-specific in vitro disease models and cutting-edge computational tools for data integration, enhancing our understanding of complex PD mechanisms. To explore common biomedical features across monogenic PD forms, we developed a knowledge graph (KG) by integrating previously published high-content imaging and RNA sequencing data of PD patient-specific midbrain organoids harbouring LRRK2-G2019S, SNCA triplication, GBA-N370S or MIRO1-R272Q mutations with publicly available biological data. Furthermore, we generated a single-cell RNA sequencing dataset of midbrain organoids derived from idiopathic PD patients (IPD) to stratify IPD patients within the spectrum of monogenic forms of PD. Despite the high degree of PD heterogeneity, we found that common transcriptomic dysregulation in monogenic PD forms is reflected in glial cells of IPD patient midbrain organoids. In addition, dysregulation in ROBO signalling might be involved in shared pathophysiology between monogenic PD and IPD cases.
帕金森病（PD）是一种进行性神经退行性疾病，目前尚无有效治疗方法。神经科学和系统生物医学的进展使得现在能够使用复杂的患者特异性体外疾病模型和前沿的计算工具进行数据整合，从而增强我们对复杂的帕金森病机制的理解。为了探索单基因帕金森病形式之间的共同生物医学特征，我们通过整合先前发表的携带LRRK2-G2019S、SNCA三倍体、GBA-N370S或MIRO1-R272Q突变的帕金森病患者特异性中脑类器官的高内涵成像和RNA测序数据与公开可用的生物学数据，构建了一个知识图谱（KG）。此外，我们生成了来自特发性帕金森病患者（IPD）的中脑类器官的单细胞RNA测序数据集，以便在单基因帕金森病形式的范围内对IPD患者进行分层。尽管帕金森病具有高度异质性，但我们发现单基因帕金森病形式中常见的转录组失调反映在IPD患者中脑类器官的神经胶质细胞中。此外，ROBO信号通路的失调可能参与单基因帕金森病和IPD病例之间共同的病理生理学过程。
