Fig. 1: Aberrant AS in HD mice. | Nature Neuroscience

Fig. 1: Aberrant AS in HD mice.

From: Aberrant splicing in Huntington’s disease accompanies disrupted TDP-43 activity and altered m6A RNA modification

Fig. 1

a, Schematics of detection of alternatively spliced exons in HD mouse models with RASL-seq98 and rMATS60. b, Altered exon (AE) events annotated by rMATS: inclusion (IN) or exclusion (EX) detected in 3mos R6/2 cortex (left) and using two published HD RNA-seq datasets from Labadorf et al.78 and Al-Dalahmah et al.63 (prefrontal cortex BA9, grade III/IV, 20 HD, 49 controls; anterior cingulate cortex, grade III/IV, six HD, six controls). Top-ranked HOMER enriched motif for each dataset is shown at the bottom. Splicing events were filtered for FDR < 0.05. c, Heatmap showing the detection of the short isoform (excluded exon) and long isoform (included exon) from RASL-seq in cortex from the R6/2, Q175 and Q150 HD mouse models. Gradient scale represents z-scores of normalized gene counts. NT, non-transgenic control for the R6/2; WT, wild type; HET, heterozygous (Q7/Q175, Q7/Q150); HOMO, homozygous (Q175/Q175, Q150/Q150). d, Left: single-nuclei sequencing validation; cell type classification of total nuclei sequenced from the striatum of 3mos R6/2. Right: bar graphs show nuclei counts from single-nuclei sequencing and number of significant (P < 0.05) splicing events detected in cell types from DESJ-detection66. From top to bottom: Astro, astrocytes; Inhib, inhibitory neurons; microglia; Oligo, oligodendrocytes; OPC, oligodendrocyte progenitor cells; premyelin cells; and vascular cells. e, Pie chart showing the detection of significant excluded exons in PacBio Iso-seq long-read sequencing. UE, upstream exon; DE, downstream exon; IN, included exon; EX, excluded exon. f, Canonical binding motif for TDP-43 (UG rich) and METTL3 (DRACH).

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