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Updated: Jan 8, 2026

Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures

Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures

Published on: November 11, 2016

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.

|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.

Keywords:

3D organoids CP: developmental biology CP: metabolism SC-β cell maturation cell replacement therapy circadian clock glucose-stimulated insulin secretion metabolic synchronization β-cell energetics

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Last Updated: Jan 8, 2026

Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures

Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures

Published on: November 11, 2016

In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells

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Published on: September 28, 2017

Monitoring Cell-autonomous Circadian Clock Rhythms of Gene Expression Using Luciferase Bioluminescence Reporters

Monitoring Cell-autonomous Circadian Clock Rhythms of Gene Expression Using Luciferase Bioluminescence Reporters

Published on: September 27, 2012

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.