Fig. 3: APOE4 disrupts astrocyte priming and its ability to promote microglial Aβ42 phagocytosis.
From: Astrocyte priming enhances microglial Aβ clearance and is compromised by APOE4
A Number and ontology of genes upregulated by Poly I:C treatment and subsequently downregulated during recovery in APOE4 hiPSC-derived astrocytes. B Changes in IL-6, IL-1β, and TNFα transcript levels by Poly I:C treatment, recovery, and second Poly I:C treatment. N = 24, from four independent batches. C Genes with increased transcripts upon second Poly I:C treatment induced by immune priming and their gene ontology. Differentially expressed genes (DEGs) were identified using Cuffdiff. Statistical significance was determined by adjusted q-values (<0.05). D Reduced increase in IL-6, IL-1β, and TNFα transcript levels in primed APOE4 astrocytes compared to APOE3 astrocytes by the second Poly I:C challenge. N = 24 (IL-6 and TNFα) and N = 22 (IL-1β), derived from four independent batches. E Changes in cytokine secretion patterns in primed APOE4 astrocytes compared to non-primed astrocytes. Cytokines that were significantly increased or decreased are indicated in red and blue, respectively. In each experiment, three samples are pooled, and the entire experiment is repeated three times using cells derived from independent batches. F Increased IL-1β transcript levels in primed APOE4 astrocytes in response to Aβ42. N = 6, from three independent batches. G Ontology analysis of genes uniquely upregulated by Aβ42 in primed APOE4 astrocytes compared to non-primed astrocytes. H Ontology analysis of genes uniquely downregulated by Aβ42 in primed APOE4 astrocytes compared to non-primed astrocytes. DEGs were identified using Cuffdiff. Statistical significance was determined by adjusted q-values (<0.05). I Increased Aβ42 uptake capability in primed APOE4 astrocytes compared to non-primed astrocytes. N = 11, from three independent batches. J Decreased microglial Aβ42 uptake in response to astrocyte-conditioned media (ACM) from primed APOE4 astrocytes exposed to Aβ42. N = 20, from two independent batches. Scale bar=5 μm. **p < 0.01, ***p < 0.001, ****p < 0.0001; ns, not significant. (One-way ANOVA test followed by Tukey’s post hoc analysis or two-tailed Student’s t-test). Exact P values are provided in the Source Data. Error bar ± S.E.M.
