Extended Data Fig. 8: Investigating ApoE4 and LRP1 in Aβ and Tau Propagation through Transcriptomic Comparisons and RAP Inhibition.
From: Differentiating visceral sensory ganglion organoids from induced pluripotent stem cells
(a) Quantifications of proportions of identified VSN subclusters among E3 and E4 VSN. (b) UMAP presenting E3 and E4 sample for VSN cluster. (c, d) UMAPs for APOE (c) and LRP1 expression (d) among VSN cluster. (e-g) Expressions of gene sets among GO term: Cholesterol Biosynthetic process (e), Regulation of Autophagy (f) and Chromatin Organization (g) among each sample. (h) Schematic explaining mechanism of RAP working on LRP1 of i-VSN neurite. Representative images of FITC-oAβ (i) and Atto-499 tauPFF (k) before and after treatment of RAP on i-VSN (TUJ1, yellow). Normalized propagation ratio of FITC-oAβ (j) (n = 9 for E4 RAP- and n = 11 for E4 RAP+ among 4 independent differentiations each) and Atto-488 tauPFF (l) (n = 10 for E4 RAP- and n = 12 for E4 RAP+ among 4 independent differentiations each) were shown as bar graphs. RAP, receptor-associated protein. Scale bars: 20 µm. (a) two-sided chi-square test (j and k) two-sided student t test. *P < 0.05, ***P < 0.001. All data were presented as mean ± SEM.
