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. 2023 Nov 13;26(12):2104–2121. doi: 10.1038/s41593-023-01480-8

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 7 — a,b, KEGG pathway enrichment dot-plot of top 20 pathways significantly enriched for DE genes of neuronal cluster 1 in PS19-E4-S/S (a) or PS19-E4-R/S (b) versus PS19-E4 mice at 10 months of age. c,d, KEGG pathway enrichment dot-plot of top 20 pathways significantly enriched for DE genes of neuronal cluster 7 in PS19-E4-S/S (c) or PS19-E4-R/S (d) versus PS19-E4 mice at 10 months of age. e,f, KEGG pathway enrichment dot-plot of top 20 pathways significantly enriched for DE genes of neuronal cluster 28 in PS19-E4-S/S (e) or PS19-E4-R/S (f) versus PS19-E4 mice at 10 months of age. g, Dot-plot normalized average expression of selected homeostatic and disease-associated oligodendrocyte (DAO) marker genes for oligodendrocyte clusters 2, 3, and 9. h, Volcano plot for top DE genes of oligodendrocyte cluster 9 versus cluster 2. i, Volcano plot for top DE genes of oligodendrocyte cluster 9 in PS19-E4-S/S versus PS19-E4 mice at 10 months of age. j, Representative images of Kirrel3⁺ Olig2⁺ oligodendrocytes in the hippocampus of 10-month-old PS19-E4 and PS19-E4-S/S mice at 10 months of age. Scale bars are 25 µm. k, Quantification of the number of Kirrel3⁺ Olig2⁺ oligodendrocytes (per mm²) within the dentate gyrus of hippocampus in 10-month-old PS19-E4 (n = 10) and PS19-E4-S/S (n = 10) mice at 10 months of age. In a–f, P-values are based on a two-sided hypergeometric test and are adjusted for multiple testing using the Benjamini-Hochberg method. Gene ratio represents the proportion of genes in the respective gene set that are deemed to be differentially expressed using the two-sided Wilcoxon Rank-Sum test as implemented in the FindMarkers function in Seurat. In h,i, horizonal dashed line indicates p-value = 0.05 and vertical dashed lines indicate log₂ fold change = 0.4. All error bars represent s.e.m. Difference between groups in k was determined by unpaired, two-sided Welch’s t-test. DE, differentially expressed; NS, nonsignificant; FC, fold change. For details of the analyses, see Methods.

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