Genome-edited human stem cell-derived beta cells: a powerful tool for drilling down on type 2 diabetes GWAS biology.

摘要: Type 2 diabetes (T2D) is a disease of pandemic proportions, one defined by complex aetiological mix genetic, epigenetic, environmental, and lifestyle risk factors. Whilst the last decade T2D genetic research has identified more than 100 loci showing strong statistical association with susceptibility, our inability to capitalise upon these signals reflects, in part, lack appropriate human cell models for study. This review discusses impact two complementary, state-of-the-art technologies on research: generation stem cell-derived, endocrine pancreas-lineage cells editing their genomes. Such facilitate investigation diabetes-associated genomic perturbations physiologically representative context allow role both developmental adult islet dysfunction pathogenesis be investigated. Accordingly, we interrogate that patient-derived induced pluripotent are playing understanding cellular monogenic diabetes, how site-specific nucleases such as clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system helping confirm genes crucial pancreas development. We also highlight novel biology gleaned absence patient lines, including an ability model whole phenotypic spectrum phenotypes occurring utero cells, interrogating non-coding ‘islet regulome’ disease-causing perturbations, other types aberrant glycaemia. article aims reinforce importance investigating reflecting species, context, time point, tissue type.