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Updated: Jan 12, 2026

Differentiation of Human Pluripotent Stem Cells Into Pancreatic Beta-Cell Precursors in a 2D Culture System
Published on: December 16, 2021
Circadian regulation of insulin secretion in transplanted human stem cell-derived pancreatic β-cells
Satish K Sen1, Zenith Khashim1, Sharath Shivakumar Belame1
1Department of Physiology and Biomedical Engineering, Mayo Clinic School of Medicine, Rochester, MN, USA.
Abstract:
Cell replacement strategies utilizing stem cell-derived pancreatic β-cells (SCβ-cells) hold therapeutic potential for patients with diabetes. However, little is known about how endogenous (host) and exogenous (transplant) circadian systems interact to influence the engraftment and function of SCβ-cells. We report that differentiation of SCβ-cells in vitro is associated with the induction of key circadian clock genes known to regulate insulin secretion. Upon transplantation into severe combined immunodeficiency (SCID)-beige mice, SCβ-cells exhibit circadian rhythms in glucose-stimulated insulin secretion optimized to the host's active circadian phase. Furthermore, disrupting the host's circadian rhythms abolishes circadian regulation and the overall functional capacity of transplanted SCβ-cells. These observations suggest that the host's circadian system entrains SCβ-cell function to optimize the circadian control of insulin secretion.
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