Single cell RNA sequencing profile of 60 day old human iPSC-derived midbrain organoids from healthy individual, Parkinson’s disease patient (Miro1 p.R272Q mutation) and its isogenic control

Use of patient specific models, such as midbrain organoids, have shown to be valuable tools to models Parkinson’s disease as well as to identify novel pathological cellular and molecular mechanisms. In here, we used single cell RNA sequencing analysis of 60 day old midbrain organoids obtained from a Parkinson’s disease patient carrying the p.R272Q Miro1 mutation, its isogenic control and a healthy control to explore the effect of RhoT1 gene in different cellular populations present within the midbrain organoids (e.g. dopaminergic neurons, astrocytes) and the subsequent effect on the PD pathology. Midbrain organoids generated from iPSC obtained from a Parkinson's disease patient carrying the Miro1 p.R272Q mutation, its respective isogenic control and from a healthy age and sex-matched donor were used. The midbrain organoids were culture for 60 days and then, dissociated into single cells and used for scRNA-seq analysis.

患者特异性模型（如中脑类器官（midbrain organoids））的应用已被证实是研究帕金森病（Parkinson’s disease, PD）、挖掘全新病理细胞与分子机制的极具价值的工具。本研究中，我们针对携带p.R272Q Miro1突变的帕金森病患者、其同基因对照（isogenic control）以及健康对照的60日龄中脑类器官开展单细胞RNA测序（single cell RNA sequencing, scRNA-seq）分析，以探究RhoT1基因对中脑类器官内不同细胞群（如多巴胺能神经元（dopaminergic neurons）、星形胶质细胞（astrocytes））的影响，及其对PD病理进程的后续作用。本研究使用的中脑类器官，均源自携带Miro1 p.R272Q突变的帕金森病患者的诱导多能干细胞（induced pluripotent stem cells, iPSC）、其对应的同基因对照，以及年龄和性别匹配的健康供体的诱导多能干细胞。将上述中脑类器官体外培养60天后，解离为单个细胞并用于单细胞RNA测序分析。