Mapping human dopamine neuron diversity at single-cell resolution for enhanced stem cell therapy in Parkinson's Disease

The use of stem cells in the clinic is almost within touching distance, and groundbreaking research in the last decade has demonstrated the therapeutic effect of dopamine (DA) neuron differentiated from hPSC in cell replacement for the treatment of Parkinsonʼs disease (PD). However human DA neurons in midbrain constitute a heterogeneous group of cells comprising different DA neuron subtypes with different function and vulnerability to PD but the molecular features associated have not yet been fully identified.
The project's overall aim is to model in vivo human DA neuron specification, innervation and diversity upon stem cell transplantation. We will use single cell multi-omics to provide a molecular map of human DA neurons after functional maturation in a pre-clinical rat PD model.