Reference genomes are foundational to modern genomics. Our growing understanding of genome structure leads to continual improvements in reference genomes and new genome "builds" with incompatible coordinate systems. We quantified the impact of genome build on germline and somatic variant calling by analyzing tumour-normal whole-genome pairs against the two most widely used human genome builds.
View Article and Find Full Text PDFRestoring functional β cell mass is a potential therapy for those with diabetes. However, the pathways regulating β cell mass are not fully understood. Previously, we demonstrated that Sox4 is required for β cell proliferation during prediabetes.
View Article and Find Full Text PDFAims/hypothesis: Pancreatic islets depend on cytosolic calcium (Ca) to trigger the secretion of glucoregulatory hormones and trigger transcriptional regulation of genes important for islet response to stimuli. To date, there has not been an attempt to profile Ca-regulated gene expression in all islet cell types. Our aim was to construct a large single-cell transcriptomic dataset from human islets exposed to conditions that would acutely induce or inhibit intracellular Ca signalling, while preserving biological heterogeneity.
View Article and Find Full Text PDFAims/hypothesis: While pancreatic beta cells have been shown to originate from endocrine progenitors in ductal regions, it remains unclear precisely where beta cells emerge from and which transcripts define newborn beta cells. We therefore investigated characteristics of newborn beta cells extracted by a time-resolved reporter system.
Methods: We established a mouse model, 'Ins1-GFP; Timer', which provides spatial information during beta cell neogenesis with high temporal resolution.