Patient-derived induced pluripotent stem cells for precision modelling of monogenic beta cell disorders.

Over the past several years, research and technologies involving patient-derived induced pluripotent stem cells (iPSCs) have rapidly advanced, enabling the study of various disease pathologies, including rare pathologies like monogenic disorders of beta cell function. iPSCs offer a unique model to study monogenic beta cell disorders such as Maturity-onset diabetes of the young (MODY) and congenital hyperinsulinism as they can be derived directly from patients with novel genetic variants and then differentiated into pancreatic progenitors and beta cells. Studies have used iPSC-derived SC-islets to demonstrate how transcription factor dysfunction can perturb insulin secretion, beta cell maturation, and endocrine lineage specification in MODY subtypes. Additional studies in congenital hyperinsulinism have utilized iPSC-derived SC-islets to model disease-specific hallmarks such as excess insulin secretion and increased beta cell proliferation. These studies provide the foundation for future studies using iPSC-derived SC-islets as a platform for elucidating mechanisms of how single-gene variants disrupt beta cell specification, maturation, and survival.