Single Cell Transcriptomics Identifies Stem Cell-Derived Graft Composition in a Model of Parkinson's Disease

Cell replacement is a long-standing and realistic goal for the treatment of Parkinson's disease (PD). Cells for transplantation can be obtained from fetal brain tissue or from stem cells. However, after transplantation dopamine (DA) neurons are a minor component of grafts and it has remained difficult to determine the identity of other cell types. Here, we report analysis by single cell RNA sequencing (scRNA-seq) combined with comprehensive histological analyses to characterize intracerebral grafts from human embryonic stem cells (hESCs) and fetal tissue after functional maturation in a pre-clinical rat PD model. We show that neurons and astrocytes are major components in both fetal and stem cell-derived grafts. Additionally, we identify a cell type closely resembling a class of newly identified perivascular-like cells in stem cell-derived grafts. Thus, this study uncovers previously unknown cellular diversity in a clinically relevant cell replacement PD model. Overall design: Single cell RNA sequencing to characterize fetal and clinical grade ventral midbrain human embryonic stem cells after long-term survival in a pre-clinical rat model of PD.