Extended Data Fig. 1: T1D pathways are upregulated in Mettl14 deficient mouse β-cells and pre-diabetic NOD β-cells show enrichment in pathways associated with Type 1 diabetes (related to Fig. 1).
a, Diagram of differentially expressed genes in Mettl14 KO β-cells compared to controls. b, Pathway enrichment analyses of genes upregulated in Mettl14 KO β-cells compared to controls (Controls, n = 4 pools, 2 animals/pool; M14KO, n = 4 pools, 4 animals/pool). c, Body weight of NOR and NOD females at 4- or 8-weeks of age (n = 6 mice/group). d, Random-fed serum glucose levels of NOR and NOD females at 4- or 8-weeks of age (n = 6 mice/group). e, Representative FACS sorting strategy to deplete CD45 positive cells, and obtain an enriched β-cell population based on size, granularity, and autofluorescence (FITC) from NOD female mice. f, Immunofluorescence staining of sorted β- and non-β-cell fractions showing insulin staining in red, glucagon in green, and somatostatin in blue (n = 3 independent experiments/group). Scale bar = 20μM. g, PCA plot of RNA-seq samples of 4- or 8-week-old FACS sorted β-cells or non-β-cells (n = 3 pools of 3 mice per pool). h, Heat-map representation of islet identity genes, showing enrichment for β cell identity genes in the β-cell fraction compared to non-β-cells. i, Heat-map of represented genes associated with Type 1 diabetes, innate immunity, and antigen processing and presentation and upregulated in pre-diabetic 8-week-old β-cells compared to 4-week-old. All samples in each panel are biologically independent. Data were expressed as means ± SEM. Heat maps represent clipped Z-scored log CPM. Statistical analyses were performed using the Benjamini-Hochberg procedure and genes were filtered for FDR<0.05 or 0.10 in ‘a’. P values of pathway enrichment analysis were calculated according to the hypergeometric test based on the number of physical entities present in both the predefined set and user-specified list of physical entities. Data in ‘a’ and ‘b’ were downloaded and reanalyzed from dataset GSE132306 (ref. 35). Source numerical data are available in source data.
