Fig. 4: scRNA-seq of AstTau reveals dynamic transcriptional response to oTau-induced pathology.
From: Single cell transcriptomic profiling of a neuron-astrocyte assembloid tauopathy model
a UMAP projection of 130,605 single-cell transcriptomes colored by conditional timepoints across the 7–21 DIV3D control and AstTau time course (blue and orange gradients, respectively) highlighting model integration and trajectory. b Percent composition of cell-type clusters in control and AstTau across the 7–21 DIV3D time course indicating loss of EX_NEU and expansion of the ASC compartment in AstTau. c Top 25 up- and downregulated DEGs in AstTau by fold change (log2FC) across the 7–21 DIV3D time course in EX_NEU, IN_NEU, and ASC. 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. d, e Single-cell average gene expression in control (blue) and AstTau (orange) ASC populations at 21 DIV3D highlighting the correlation of AstTau ASC transcriptomic signature with published astrocytic signatures including A1 toxic and A2 protective astrocytes (ref. 71), AD-associated astrocytes (ref. 61), and the Reactome HSF1 pathway (d) and EX_NEU and IN_NEU populations at 21 DIV3D highlighting the correlation of AstTau neurons with published single-nuclei AD neuronal signatures (ref. 72), and the cell-type differential response in the HALLMARK TNFα signaling via NFKB neuroinflammatory response and concurrent response in the GO Cytosolic Ribosomal pathway (e). (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. Source data are provided as a Source Data file.
