Extended Data Fig. 7: TET2 expression is increased in neurons of PD-relevant models and PD patient neurons.

a, TET2 transcript levels in induced dopaminergic (iDA) neurons of PD patients and controls (n = 8 control fibroblasts, 7 PD fibroblasts, 8 control iDA neurons, 9 PD iDA neurons). b, TET2 transcript levels in bulk subventricular zone (SVZ), isolated neuronal stem cells (NSCs), and isolated microglia cells from PD patients and controls (n = 3 control SVZ, 4 PD SVZ, 4 control NSCs, 5 PD NSCs, 2 control microglia, 4 PD microglia). c, d, Tet2 transcript levels in neurons of PD-relevant models. Tet2 mRNA levels in dopaminergic neurons of mice treated with (c) MPTP (n = 4 saline, 4 MPTP) or (d) 6-OHDA (n = 4 non-injected side, 4 6-OHDA). a‒d, Transcriptomic analyses of RNA-seq datasets were performed using a generalized linear model adjusting for sources of unknown variation, with contrast fit for group-wise comparisons. TET2 transcript levels in counts per million (cpm) with nominal P < 0.05 significance. Datasets: GSE54795, GSE108370, GSE125239, and GSE130752. e, TET2 mRNA depletion by siRNA in the neuronal cell model, SH-SY5Y cells. TET2 mRNA transcript levels in SH-SY5Y cells 72 h after incubation with TET2 siRNA (TET2i) or non-target control (NT). TET2 mRNA levels determined by qPCR and normalized to housekeeping genes B2M, HPRT, and RPL13 (n = 6 NT, 6 TET2i samples). ****P = 10⁻⁵, by two-tailed, unpaired equal variance t-test. a‒e, Boxplot center line is the mean, the bounds of the box are the lower and upper quartiles, and the whiskers extend to minimum and maximum data points within 1.5 times the interquartile range. f, Cytosine modification changes in response to TET2 mRNA depletion in vitro. Differentially modified cytosines induced by TET2 reduction in SH-SY5Y cells were identified using logistic regression (n = 8 NT, 8 TET2i). Enrichment in hypomethylation in response to TET2 inactivation determined by Fisher’s exact test with odds ratio (OR) and P = 10⁻²³⁴ for significance of enrichment. The proportion of significantly hypomethylated (blue) and hypermethylated (red) cytosines induced by TET2 inactivation is shown, with all cytosines in the analysis (background) in gray.