AUTHOR=Huang Jianjun , Liu Li , Qin Lingling , Huang Hehua , Li Xue 

TITLE=Single-Cell Transcriptomics Uncovers Cellular Heterogeneity, Mechanisms, and Therapeutic Targets for Parkinson’s Disease

JOURNAL=Frontiers in Genetics

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.686739

DOI=10.3389/fgene.2022.686739

ISSN=1664-8021

ABSTRACT=Objective: This study aimed to exploit cellular heterogeneity for revealing mechanisms and identifying therapeutic targets for Parkinson’s disease (PD) via single cell transcriptomics.
Methods: Single-cell RNA-sequencing (scRNA-seq) data of midbrain specimens from PD and healthy individuals were obtained from the GSE157783 dataset. After quality control and preprocessing, principal component analysis (PCA) was presented. Cells were clustered with the Seurat package. Cell clusters were labeled by matching marker genes and annotations of brain in the CellMarker database. The ligand-receptor networks were established and the core cell cluster was selected. Biological functions of differentially expressed genes in core cell cluster were analyzed. Up-regulated marker genes were identified between PD and healthy individuals, which were measured in 18 PD patients’ and 18 healthy individuals’ blood specimens through RT-qPCR and western blotting.
Results: The first 9 PCs were determined, which can better represent the overall change. Five cell clusters were identified, including oligodendrocytes, astrocytes, neurons, microglial cells, and endothelial cells. Among them, endothelial cells were the core cell cluster in the ligand-receptor network. Marker genes of endothelial cells possessed various biological functions. Among them, five marker genes (ANGPT2, APOD, HSP90AA1, HSPA1A and PDE1C) were up-regulated in PD patients’ than healthy individuals’ endothelial cells, which were confirmed in PD patients’ than healthy individuals’ blood specimens.
Conclusion: Our findings revealed the cellular heterogeneity of PD and endothelial cells could play a core role in cell-to-cell communications. Five up-regulated marker genes of endothelial cells could be underlying therapeutic targets of PD, which deserved more in-depth clinical research.