Fig. 2: Lipid alterations in patient-derived neurons expressing differing alpha-synuclein (αSyn) doses.
Lipidomic heat maps showing Log(2) fold changes (A) all lipid groups and selected individual lipid species of: B Ceramide (Cer), C dihydroceramide (dhCer), D dihydrosphingomyelin (dhSM) and E sphingomyelin (SM) in induced pluripotent stem cell (iPSC)-derived neurons carrying either αSyn knock out (αSyn-KO) or αSyn duplication (αSyn-Dupl), normalized to age-matched neurons expressing endogenous αSyn levels (Ctrls) after 30 days of directed differentiation. F Relative concentrations of total sphingolipids and G sphingolipids containing long-chain fatty acids (22:1 to 26:1) are presented. Lipidomic heat maps displaying Log (2) fold changes in selected phospholipids: H Phosphatidylcholine (PC), I Plasmalogen phosphatidylethanolamine (PEp), J Phosphatidylserine (PS), K Phosphatidylglycerol (PG). Relative concentrations of L total phospholipids and M phospholipids containing polyunsaturated fatty acids (PUFAs, 40:4 to 42:7) are presented. All data are normalized to the concentrations in Ctrl samples. Data are presented as the mean ± SEM of at least 4 independent biological replicates (n) analyzed by an ordinary two-way analysis of variance ANOVA, with the interaction of cell line x lipid group given in: F Total sphingolipids: Interaction (F(16,99) = 5.462; ****p < 0.0001), G Sphingolipids containing long-chain fatty acids: Interaction (F(16,99) = 1.522; p = 0.1068), Row Factor (cell line) (F(2,99) = 19.09; ****p < 0.0001); (L) Total phospholipids, Interaction (F(18,110) = 2.485; **p=0.002); (M) Phospholipids containing long-chain fatty acids: Interaction (F(18,110) = 5.215; ***p < 0.0001). For post-hoc analyses (F, G & L, M) a Tukey’s multiple comparison test was used with single pooled variance, *p < 0.05, **p < 0.01, ***p < 0.001 ****p < 0.0001.
