Fig. 1. Patient and sample distributions of six transcriptomic datasets of Parkinson’s disease reprogrammed neurons.

A The transcriptome data analyzed in the present study were collected across six different datasets and originate from the reprogrammed neurons of n = 25 healthy individuals, n = 7 patients with known mutations in PD genes, and n = 10 patients with a sporadic form of the disease (n = 42 unique subjects total). B Overview of tissue culture trajectories used in six reprogramming studies to generate in vitro midbrain-like neurons from PD patient- and healthy subject-derived fibroblasts (see Methods for details). Pie charts on the left summarize the number of subjects from which neurons were derived, color-coded by disease phenotype and mutation type as shown in (A). Neuron cultures were generated via induced pluripotent stem cell (iPSC) technology (n = 4 studies) or by direct conversion of fibroblasts into induced neurons (iNs, n = 2 studies), and neuronal transcriptome data was obtained by single-cell or bulk RNA-seq (n = 2 and 4 studies, respectively). The trajectory color reflects the combinatory choice of the reprogramming and sequenced method used (orange: single-cell iPSC neuron datasets; blue: bulk iPSC neuron datasets; green: bulk iN datasets). Single-cell RNA-seq was performed on (i) functionally mature (AP Types 4 + 5) single neurons collected after patch-clamp recording (PatchSeq, n = 44) or on (ii) wild-type and isogenic SNCA-A53T neurons harvested using 10X Chromium technology³⁸. The two iN datasets enriched for successfully reprogrammed (i.e., PSA-NCAM-positive) neurons using fluorescence-activated cell sorting (FACS). The bulk-iPS-Dopa and bulk-iN-Dopa studies used an optimized differentiation protocol to generate a high proportion of midbrain dopaminergic neurons. Pie charts on the right indicate the number of cells or samples sequenced per disease state and/or mutation type. A total of 5,359 single neurons and 80 neuronal bulk samples were analyzed.