Extended Data Fig. 7: Single-cell RNA-seq of Haster^pKO islets.

a, Clusters of islet cells from female Haster^pKO (4961 cells from triplicates for Seurat; 4456 for scVI) and controls (4646 cells from triplicates for Seurat; 4460 for scVI) determined by Seurat (t-SNE projection) or scVI (UMAP projection). b, scVI UMAP and Seurat t-SNE projections showing hormone expression. c, Cell type assignment based on marker gene expression. d, Haster and Hnf1a mRNA (log normalized UMI count) in different cellular populations of control and Haster^pKO islets (Seurat). e, HNF1A-regulated gene expression (average Z-score) showing lower expression of HNF1A-regulated genes in the HASTER^pKO-enriched β cell cluster (HNF1A^low) and high expression of HNF1A-regulated genes in other β cells in HASTER^pKO cells. f, Relative proportions of β cells present in the HASTER^pKO-enriched HNF1A^low β cell cluster. n = 3 mice per genotype. Mean ± s.d., two-tailed Student’s t-test. We note these proportions are lower than observed in situ, plausibly because Hnf1a^-/- islets have a marked propensity to dissociate upon collagenase digestion, which is expected to cause negative selection of HNF1A-deficient cells after digestion and FACS sorting of single cells. g, HNF1A-regulated gene expression (average Z-score) for different cell types in individual samples (Seurat). h, Histograms showing the distribution of HNF1A-regulated gene expression (average Z-score) for β, α and δ cells (Seurat). Bins = 40. The variance of HNF1A-regulated gene expression increased in Haster^pKO β, α and δ cells, showing that HNF1A-regulated genes are either upregulated or downregulated in islet cells. Levene test P-values.

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