Fig. 3: The transcriptome of sorted human alpha and beta cells.
a, Venn diagram showing the number of overlapping (12,384) and uniquely expressed protein-coding genes in human alpha and beta cells, with 617 and 492 genes, respectively, requiring ≥20 mean normalized counts in ≥80% of the samples. b,c, Gene ontology of the protein-coding genes uniquely expressed in human alpha (b) or beta (c) cells, showing significantly enriched pathways (q < 0.05). d,e, The 20 most abundantly expressed genes in alpha (d) and beta (e) cells of 16 donors. Data are presented as the mean ± s.e.m. Women and men are represented by filled and open circles, respectively. f, Volcano plot showing DEGs at q < 10 × 10−8 and q < 0.05, based on DESeq2 (ref. 82), in human alpha versus beta cells sorted from the same islet preparations (n = 16 donors). g–o, Alpha versus beta cell DEGs based on DESeq2 (ref. 82; ***q < 0.001, n = 16 donors) that also have significant DMRs (q < 0.05, based on dmrseq25): TM4SF4 (g), F10 (h), IRX2 (i), FEV (j), LDHA (k), ADCY2 (l), NR3C1 (m), GLIS3 (n) and SYT13 (o). Data are presented as the mean ± s.e.m. Women and men are represented by filled and open circles, respectively. p, Selected KEGG pathways with significant enrichment (q < 0.05 based on WebGestalt analysis with correction for multiple testing) of DEGs in alpha versus beta cells with q < 10 × 10−8. q, 186 of 849 genes (22%) with T2D-associated SNPs identified by GWAS2 overlapped with the top DEGs (q < 10 × 10−8, based on DESeq2)82 in human alpha versus beta cells (HES = 1.67, P = 1.07 × 10−31, based on one-tailed hypergeometric test). Exact P values for the expression data and DEGs are found in Supplementary Table 6. P/q values for b, c and f–p were corrected for multiple testing.
