Fig. 7: scRNA-seq transcriptomic modulation supports PU-H71 reversal of the pathological molecular phenotype in AstTau.
From: Single cell transcriptomic profiling of a neuron-astrocyte assembloid tauopathy model
a UMAP projection of 130,605 cells colored by conditional timepoints across the 7–21 DIV3D control and AstTau time course with vehicle or PU-H71 treatment (blue, orange, green, purple gradients, respectively) highlighting model integration and trajectory. b Top 25 up and downregulated DEGs between control and AstTau at 7 DIV3D and 21 DIV3D +/− PU-H71 treatment in EX_NEU, IN_NEU, and ASC, highlighting the similarity between 7 DIV3D and 21 DIV3D with PU-H71. Transcripts associated with the GO Cytosolic Ribosomal, HALLMARK TNFα Signaling via NFKB, and the REACTOME HSF1 Activation pathways are highlighted in green, purple, and red, respectively. c, d Single-cell average gene expression in the oTau-/PU-H71- (blue), oTau+/PU-H71-(orange), oTau-/PU-H71 + (green), and oTau+/PU-H71 + (purple) ASC populations (c) highlighting the impact of PU-H71 treatment on the A1 toxic and A2 protective astrocytic signature71, and NEU populations (d) highlighting the impact of PU-H71 treatment on the neuronal signatures including single-nuclei AD neuronal signatures (ref. 72), the HALLMARK TNFα signaling via NFKB neuroinflammatory response, and the GO Cytosolic Ribosomal at 21 DIV3D. (t.test, ns: P > 0.05, *P < = 0.05, **P < = 0.01, ***P < = 0.001, ****P < = 0.0001). Inset box plots show the median, lower and upper hinges that correspond to the first quartile (25th percentile) and third quartile (75th percentile), and the upper and lower whiskers extend from the smallest and largest hinges at most 1.5 times the interquartile range. Mean values are numerically presented. e Top 25 functional gene set enrichment pathways by P value of significant upregulated DEGs (see “Methods”, P < 0.05, log2foldchange > 0.25) between AstTau and control for each timepoint in EX_NEU, IN_NEU, and ASC cell populations +/− PU-H71 presented as –log10 P value highlighting cell-type-specific pathway perturbations that are ameliorated by PU-H71 treatment. Manual annotation of shared gene set features presented for clarity. See Supplementary Fig. 10 for full annotations. Source data are provided as a Source Data file.
