Fig. 5: Different isoforms of Trem2 are up-regulated with the progression of tau pathology in TG mice. | Nature Communications

Fig. 5: Different isoforms of Trem2 are up-regulated with the progression of tau pathology in TG mice.

From: Long-read transcript sequencing identifies differential isoform expression in the entorhinal cortex in a transgenic model of tau pathology

Fig. 5

A Cluster dendrogram depicting the repertoire of Trem2 transcripts identified in the rTg4510 cortex. Each row and column corresponds to a distinct isoform and known exon, respectively. Colors refer to the presence of alternative splicing events (ES exon skipping, IR intron retention). B Heatmap depicting the expression of all Trem2 isoforms. Each row refers to an isoform, colored by structural category (FSM – dark blue, ISM – light blue, NIC – pink, NNC – light pink), and each column refers to a sample with the genotype (WT – gray, TG – red) and age (2 months – white, 4 months – light gray, 6 months – dark gray, 8 months – black) shown. C Visualization of the reference and selected novel Trem2 isoforms coloured by structural category (pink – NIC, light pink – NNC), including a novel isoform incorporating all six known exons (All), novel isoforms with alternative 5’ and 3’ splice sites (A5A3), exon skipping (ES), and novel exons located upstream (NE) and within the gene (CE). Shown in the final panel are the three differentially expressed transcripts (DETs) associated with tau pathology, with colors matching F. D Box-plot of normalized read counts (TPM) of Trem2-201 and Trem2-202 transcripts detected in NeuN+ (neuron-enriched) and NeuN- (glia-enriched) nuclei populations from WT and TG mice (n = 8). E Representative immunohistochemistry staining of hippocampal tissue from rTg4510 TG mice at 8 months for Iba1 (cyan), Trem2 (red) and AT8Tau (green). Staining was repeated across 4 sections and uncropped scans are provided in Supplementary Fig. 19. F Transcript-level expression of three Trem2 DETs associated with tau pathology. (G) Trem2 gene expression in WT (gray) and TG (black) mice across age (n = 18). Isoform usage (proportion) of the three Trem2 DETs stratified by H genotype and I age (n = 18). For box-plots, the middle box represents the interquartile range (IQR), the middle line represents the median, and the whisker lines represent the minimum (quartile 1 – 1.5 × IQR) and the maximum (quartile 3 + 1.5 × IQR). Expression is derived from normalizing ONT full-length read counts.

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