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. 2024 Sep 5;7:1088. doi: 10.1038/s42003-024-06810-5

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

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Fig. 1 — a Diagram showing the experimental procedures of lipidomic analysis using the brain of 12-month-old WT and Tmem106b^−/− mice. First, targeted shotgun lipidomics were performed using 6 mice per genotype (cohort 1) to analyze 17 general lipid classes; phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylglycerol (PG), phosphatidylinositol (PI), phosphatidic acid (PA), cardiolipin (CL), lyso-phosphatidylcholine (LPC), lyso-phosphatidylethanolamine (LPE), lyso-cardiolipin (LCL), sphingomyelin (SM), ceramide (Cer), sulfatide (ST), hexosylceramide (HexCer), free cholesterol (CHL), cholesterol esters (CE), bis(monoacylglycerol)phosphate (BMP). The total number of lipid species analyzed in this study is 294. Second, ST and HexCer levels were analyzed using another cohort with 7 mice per genotype (cohort 2) to test replicability. Finally, SFC-MS/MS was performed using cohort 1 to analyze galactosylceramide (GalCer) and glucosylceramide (GlcCer) species separately. The diagram was created with BioRender.com. b Volcano plot of discovery analysis with cohort 1 showing all 294 molecular lipid species. n = 6 (3 males and 3 females) per genotype. HexCer and ST species (p < 0.05) are highlighted in red and orange, respectively. The horizontal line indicates p = 0.05. p Values were calculated using two-tailed unpaired t-test. c Heatmap of all lipid species significantly affected by TMEM106B deficiency at p < 0.05 cutoff. d Scatter plots of the sum of all species within a lipid class for each class in WT versus Tmem106b^−/−. Mean ± SEM, n = 6 (3 males and 3 females) per genotype. *p = 0.0411 (PA), *p = 0.0311 (ST), *p = 0.0279 (HexCer); two-tailed unpaired t-test.