Unveiling the effect of the Parkinson's disease related Miro1R272Q mutation in the transcriptome of human iPSC-derived dopaminergic neurons

Over the past decade evidences have been pointing in a role of RhoT1 gene (Miro1) in Parkinson's disease (PD). Miro 1 is an important part of the motor/adaptor complex and an essencial regulator of mitochondrial transport and homeostasis in neurons. In fact, our group have identify a few PD patiens carrying heterozygous mutations in the RhoT1 gene. One specific mutation, Miro1 R272Q , seems to play a important role in the pathology development. To better understand the role of Miro1 R272Q mutation in PD we used iPSC-derived doapminergic neurons. Three different cell lines, one coming from a PD patient harboring the Miro1 R272Q mutation, its respective isogenic control and a healthy individual (age- and sex- matched) were used in the study to generate dopaminergic neurons (most affected cellular population in PD). At day 30 of culture, gene expression changes caused by the Miro1 R272Q mutation were unveil using bulk RNA sequencing. The data showed a clear separation between the PD Miro1 R272Q cells and isogenc and helthy control at the PC1. Also, deregulated Go Terms such as axon, neuron projection, vesicle release, among other support the role of Miro1 R272Q mutant as important in PD pathogenecity. Overall design: 30 day old iPSC-derived dopaminergic neurons from 3 different cell lines - 1 PD patient with Miro1 R272Q mutation, 1 isogenic control, 1 healthy individual (aged- and sex-matched) - were used to assess total RNA. A total of 4 independ derivations of dopaminergic neurons for each cell line were sent to RNA-seq analysis. This allow to comprove the robustness of the model and assess the specific contribution of Miro1 R272Q mutant on the PD phenotypes observed.