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Updated: Jan 8, 2026
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Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
Published on: November 11, 2016
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DEC1 regulates human β cell functional maturation and circadian rhythm
Sam Preza1, Bliss Zheng2, Zihan Gao1
1Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Chronobiology and Sleep Institute, and Institute for Regenerative Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Cell Reports
|December 12, 2025
Summary
A key protein, DEC1, is crucial for making stem cell-derived islet organoids mature and functional for diabetes therapy. It synchronizes the circadian clock, improving insulin secretion and glucose response.
Area of Science:
- Endocrinology
- Stem Cell Biology
- Chronobiology
Background:
- Stem cell-derived islet (SC-islet) organoids hold promise for diabetes cell replacement therapy.
- Immature function of SC-islets, particularly insufficient insulin secretion, hinders their clinical application.
- The role of the β cell circadian clock in SC-islet maturation is not well understood.
Purpose of the Study:
- To investigate the role of the circadian transcription factor DEC1 in the maturation of human stem cell-derived β cells.
- To determine how DEC1 influences insulin responsiveness, glucose metabolism, and circadian regulation in SC-islets.
Main Methods:
- Generation of DEC1-ablated human pluripotent stem cells and subsequent differentiation into SC-islet organoids.
- Assessment of insulin release capacity, glucose threshold, and metabolic flux in DEC1-ablated and control SC-islets.
- Analysis of circadian rhythms, clock machinery synchronization, and expression of maturity-linked effectors.
Main Results:
- DEC1 ablation in SC-islet organoids resulted in impaired insulin release and glucose responsiveness, failing to mature in vitro and after transplantation.
- DEC1 deficiency led to blunted glycolytic and oxidative metabolism, with downregulation of maturity-linked effectors.
- Restoring metabolic flux partially rescued the functional deficits in DEC1-ablated SC-islets.
- DEC1 was essential for synchronizing circadian glucose-responsive insulin secretion and clock gene expression, promoting SC-islet maturity.
Conclusions:
- The circadian transcription factor DEC1 is a critical regulator of human β cell maturation and function in stem cell-derived islets.
- DEC1 links circadian rhythms to glucose metabolism and insulin secretion, essential for generating functional SC-islet organoids for diabetes therapy.
- Targeting DEC1 or circadian pathways may enhance the therapeutic potential of stem cell-derived islets for diabetes treatment.
Keywords:
3D organoidsCP: developmental biologyCP: metabolismSC-β cell maturationcell replacement therapycircadian clockglucose-stimulated insulin secretionmetabolic synchronizationβ-cell energeticsMore Related Videos
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