Extended Data Fig. 7. Extended analysis on the differential effects of amyloid-β plaques and soluble aggregates on microglia cell states.
a, Phenotypic trajectory followed by the human microglia transplanted in AppNL-G-F ApoE−/− and AppNL-G-F, obtained by an unbiased pseudotime ordering with Monocle 3. Proportion of cells (y-axis) present in each cell state as in Fig. 1b (rows) at different stages of the binned pseudotime trajectory (x-axis), colored by host genotypes (dots represent single mice, n = 11 AppNL-G-F, n = 6 AppNL-G-F ApoE−/−). b, c, Volcano plots showing a paired comparison between microglia transplanted in AppNL-G-F ApoE−/− and AppNL-G-F mice, coloured by (b) host genotype and (c) cluster as in Fig. 1a. The number of significant genes per condition is reported in brackets in the legend (Log2 Fold-Change threshold > 0.1). Adjusted p-value threshold < 0.05 (Wilcoxon rank-sum test, P-values adjusted with Bonferroni correction based on the total number of genes in the dataset, ns = not significant). d, Phenotypic trajectory followed by the human microglia after injection of amyloid-b oligomers (Aβο) or scrambled peptide (Scr), obtained by an unbiased pseudotime ordering with Monocle 3. Proportion of cells (y-axis) present in each cell state as in Fig. 1a (rows) at different stages of the binned pseudotime trajectory (x-axis), colored by cells genotypes (dots represent single mice, n = 7 for Scr, n = 13 Aβο). e, f, Volcano plots showing a paired comparison between microglia transplanted in AppWT mice and treated with Aβο or Scr, coloured by (e) treatment and (f) cluster as in Fig. 1a. The number of significant genes per condition is reported in brackets in the legend (Log2 Fold-Change threshold > 0.1). Adjusted p-value threshold < 0.05 (Wilcoxon rank-sum test, P-values adjusted with Bonferroni correction based on the total number of genes in the dataset, ns = not significant). Box plots in a and d, are limited by lower and upper quartiles and midline indicates median; whiskers extend from the box to the smallest or largest value no further than 1.5*inter-quartile range. Unpaired t-test with Welch’s correction, two-tailed, alpha = 0.05, significance was set as P-value < 0.05, *p < 0.05, **p < 0.01, ***p < 0.001,****p < 0.0001.