Single cell transcriptomics identifies stem cell-derived graft composition in a model of Parkinson’s disease

Cell replacement for the treatment of Parkinsonʼs disease (PD) can be obtained from fetal brain tissue or from stem cells. However, after transplantation, dopamine (DA) neurons are seen to be a minor component of grafts, and it has remained difficult to determine the identity of other cell types. Here, the authors use single-cell RNA sequencing (scRNA-seq) combined with histological analyses to characterize intracerebral grafts from ventral midbrain (VM)-patterned human embryonic stem cells (hESCs) and VM fetal tissue after long-term survival and functional maturation in a preclinical rat model of PD. Neurons and astrocytes were shown to be major components in both fetal and stem cell-derived grafts but oligodendrocytes are only detected in grafts of fetal tissue. On the other hand, a cell type closely resembling a class of newly identified perivascular-like cells is identified as a previously unknown component of hESC-derived grafts.