Fig. 1

Cell types in human substantia nigra parscompacta and their susceptibility to PD. A Schematic of the experimental design. Nuclei were isolated from sections of frozen post-mortem brain containing substantia nigra pars compacta (SNpc) from Control (14) and PD (15) donors. Sequencing libraries were then prepared using the 10X Genomics Chromium platform and sent for standard Illumina sequencing. Spatial transcriptomics was performed on slices of fresh frozen SNpc tissue; samples were taken from 3 Control donors and 3 sporadic PD patients, selected from the cohort of 29 brains used for sequencing (Supplementary Table 1). B UMAP-based clustering of 83,484 high quality nuclei obtained from 15 PD and 14 Control samples. Clusters representing neurons, oligodendrocytes (Oligo), astrocytes (Astro), microglia (Micro), oligodendrocyte progenitor cells (OPC), T cells and vascular cells (VC) were identified, based on the expression of known marker genes (see also Supplementary Fig. 1A). C UMAP showing how nuclei from PD and Control samples distribute across the different clusters. D Expression of cell markers used to identify higher level cell types in SNpc. E A pie chart showing the percentage of major cell types in our SNpc dataset. F Bar plots showing the relative number of nuclei per cluster originating from Control or PD samples against their predicted abundance (based on 47.34% of all nuclei originating from PD samples: dashed line). A Binomial test was performed to see if there is any significant divergence of cell proportions from this value, * p-value < 0.05, ** p-value < 0.0005, *** p-value < 0.00005. G Independent clustering of the spatial transcriptomics dataset. H Confirmation of cell type marker expression using spatial transcriptomics