POLR3 gene and protein expression dynamics in 4H 205 6 Intra-cluster correlation The random effects extracted from the fitted LMEMs were used to estimate the proportion of variance explained by inter-individual variability (i.e., the between donor-line specific differences) compared to within-individual variability (i.e., the residual variance or error term). Here, a higher-valued ICC indicates that a large proportion of the total variability prevalent in the gene/protein expressions, transcripts, or subunits is due to differences between donors. Consequently, a lower-valued ICC represents that most of the variability is within individuals or attributable to other unknown sources (like measurement error). The ICC formula is outlined in the Supplementary Excel file. False discovery rate The (Benjamini-Hochberg) False Discovery Rate (FDR) was utilized as a post-hoc adjustment method to address multiple hypothesis testing (i.e., to control the probability of incurring a Type 1 error) when comparing across all combinations of the different cell types. Given there are possible three tests (iPSC-NES, iPSC-neurons, and NESneurons), the adjusted significance thresholds for each rank (one, two, three) are as follows: 0.01667, 0.0333, and 0.0500. The three p-values associated with the cell-type pairwise comparisons are first sorted (in ascending order) and then compared to three adjusted thresholds (0.0167, 0.0333, and 0.0500) such that significance can be determined. FUNDING This work was supported by the European Joint Programme on Rare Diseases (EJPRD19201, NG4LEUKO) and by Netherlands Organization for Scientific Research (NWO; Gravitation: BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology; grant 024.004.012) COMPETING INTERESTS The authors declare no competing or financial interests AUTHOR CONTRIBUTIONS LK and VH designed the study. VH acquired the funding. LK performed the experiments assisted by FG, EL and NB. LK visualized the data and wrote the original draft in consultation with HvZ, VH and NW. Formal analysis was performed by HvZ
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