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. 2024 Mar 27;27(5):886–900. doi: 10.1038/s41593-024-01600-y

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© The Author(s) 2024

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 licence, and indicate if changes were made. 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/4.0/.

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Fig. 7 — a,e, Density plots displaying the average distribution of human H9-WT (n = 2) and H9-TREM2^R47H (n = 3) (a), and APOE2/2 (n = 6), APOE3/3 (n = 6) and APO4/4 (n = 6) human microglia (e) transplanted in App^NL-G-F mice. b,f, Distribution and percentage of cells across all identified clusters for H9-WT (n = 2) and H9-TREM2^R47H (n = 3) (b), and APOE2/2 (n = 6), APOE3/3 (n = 6) and APO4/4 (n = 6) (f). Dots represent single mice. c,g, Phenotypic trajectory followed by H9-WT (n = 2) and H9-TREM2^R47H (n = 3) (c), and APOE2/2 (n = 6), APOE3/3 (n = 6) and APO4/4 (n = 6) (g) human microglia obtained by an unbiased pseudotime ordering with Monocle 3. Proportion of cells (y axis) over the binned pseudotime trajectory (x axis), colored by genotypes shown in a. Dots represent single mice (*P < 0.05). d,h, Correlation of the logFC in TREM2^R47H versus H9-WT (y axis) and H9-TREM2^−/− versus H9-WT (x axis) (d), and TREM2^R47H versus H9-WT (y axis) and APOE4/4 versus APOE3/3 (x axis) (h) microglia transplanted in App^NL-G-F mice (Pearson’s correlation, R = 0.17, differentially expressed genes were adjusted using Bonferroni correction and colored as in Fig. 1b). i,j, Comparison of transcriptomic profiles of APOE4/4 (versus APOE3/3) versus APOE^−/− (versus APOE3/3) (i), and APOE4/4 (versus APOE2/2) versus APOE^−/− (versus APOE2/2) (j) microglia transplanted in App^NL-G-F mice (Pearson’s correlation, differentially expressed genes were adjusted using Bonferroni correction and colored according to clusters in Fig. 1b). Box plots in b,c,f,g are limited by lower and upper quartiles and midline indicates median; whiskers show minimum to maximum values (b,f) or extend from the box to the smallest or largest value no further than 1.5 × interquartile range (c,g). Unpaired t-test with Welch’s correction, two-tailed, alpha = 0.05, significance was set as P < 0.05 (b,c); or one-way ANOVA with Tukey’s multiple comparisons as post hoc test, alpha = 0.05, significance was set as P-adjusted value < 0.05 (f,g). In d,h,i, ‘activated’ indicates that differential expression was performed comparing reactive cell states, excluding homeostatic or transitioning clusters.