Extended Data Fig. 4: Mutant FUS-specific dysregulated RNA signature in adult motor axons of mFUSKO/hFUSR521H sciatic nerves identified using axonal spatial transcriptomics.
From: Axonal Eif5a hypusination controls local translation and mitigates defects in FUS-ALS
a, Heatmap of the top 20 DEGs between 12-month-old nontransgenic and mFUSKO/hFUSR521H motor axons. Colored scale, scaled log2-normalized counts. b, Gene ontology enrichment analysis of the most upregulated genes in mFUSKO/hFUSR521H motor axons obtained with DAVID. c, Gene ontology enrichment analysis of the most downregulated genes in mFUSKO/hFUSR521H motor axons obtained with DAVID. d, GeoMx DSP normalized counts of the indicated genes belonging to the translation machinery. Data are represented as mean ± s.e.m. (n = 4). P value = 0.031 (Eif1), not significant (other genes) using an unpaired two-tailed t test. Each data point corresponds to the measurement in one section. e, Expression pattern of the indicated genes in the motor neuron cluster obtained by applying 10x Genomics Visium spatial transcriptomics. Scales represent the log2-normalized expression. f, Violin plot of the log-normalized expression for the indicated genes in the motor neuron cluster originating from d. Data represent four biological replicates. The embedded box plots indicate the median (center line), interquartile range (25th and 75th percentiles; box edges) and whiskers extending to 1.5 times the interquartile range. g, GeoMx DSP normalized counts of the indicated genes. Data are represented as mean ± s.e.m. (n = 4). P values = not significant using unpaired two-way t test. Each data point corresponds to the measurement in one section.
