NGN3 as a mediator of human pancreatic progenitor cell competence - studying the molecular dysfunction in cells from patients with rare mutations is a powerful approach to learning about development…

The National Institute of Diabetes and Digestive and Kidney Diseases awarded Children's Hospital Los Angeles $435,907 on September 1, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to investigate NGN3's role as a mediator of human pancreatic progenitor cell competence.

The recipient will modify established male and female pluripotent stem cell lines, including patient-specific induced pluripotent stem cell lines carrying mutations in NEUROG3, to assess the role of NGN3 in establishing pancreatic progenitor cell competence. The research uses a patient-specific mutation approach to understand molecular mechanisms governing pancreatic development and disease. Findings may inform how human pluripotent stem cells differentiate into insulin-secreting beta-like cells and could provide new mechanisms to biologically target and improve beta cell differentiation and function. Improved pancreatic progenitor cell quality could enable more efficient derivation of functional, viable, glucose-responsive insulin-secreting cells for drug screening, disease modeling, and potential stem cell-derived beta cell replacement as cellular therapy for patients with diabetes.

Work is performed in Los Angeles, California. The project period runs through August 31, 2027.

NGN3 as a mediator of human pancreatic progenitor cell competence - studying the molecular dysfunction in cells from patients with rare mutations is a powerful approach to learning about development and disease. The georgia lab uses a patient-specific induced pluripotent stem cell line with a mutation in NEUROG3 to understand the mechanisms that govern pancreatic progenitor cell competence. Based on our preliminary data, we hypothesize that NEUROG3 has a previously unrecognized role during a critical window of development, to establish pancreatic progenitor cell competence. To pursue this hypothesis, we need to build tools and datasets using additional cell lines, thus making our fundings more generalizable to the larger public population. We propose to modify established male and female pluripotent stem cell lines to assess the role of NEUROG3 in establishing pancreatic progenitor cell competence. Our findings may affect the ways human pluripotent stem cells are differentiated into insulin secreting beta like cells or provide new mechanisms that biologically target and improve beta cell differentiation and function. If we can improve the quality of pluripotent stem cell derived pancreatic progenitor cells, we may be able to more efficiently derive functional, viable, glucose-responsive, functional insulin secreting cells. This could be useful for drug screening, disease modelling, and be move the field closer to developing stem-cell derived beta cell replacement as a cellular therapy for patients with diabetes.