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Chromatin dynamics reveal circadian control of human in vitro islet maturation [RNA-seq]

ABSTRACT: Chromatin dynamics reveal circadian control of human in vitro islet maturation [RNA-seq]

PROVIDER: PRJNA587101 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10384200_1.fastq.gz	Fastqsanger.gz
	SRR10384200_2.fastq.gz	Fastqsanger.gz
	SRR10384201_1.fastq.gz	Fastqsanger.gz
	SRR10384201_2.fastq.gz	Fastqsanger.gz
	SRR10384202_1.fastq.gz	Fastqsanger.gz

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Project description:Stem cell-derived islet (SC-islet) organoids offer hope for cell replacement therapy in diabetes, but their immature function remains a challenge. Mature islet function requires the β-cell circadian clock, yet how the clock regulates maturation is unclear. Here, we show that a circadian transcription factor specific to maturing SC-β cells, DEC1, regulates insulin responsiveness to glucose. SC-islet organoids form normally from DEC1-ablated human pluripotent stem cells, but their insulin release capacity and glucose threshold fail to increase during in vitro culture and upon transplant. This deficit reflects downregulation of maturity-linked effectors of glucose utilization and insulin exocytosis, blunting glycolytic and oxidative metabolism, and is rescued by increasing metabolic flux. Moreover, DEC1 is needed to boost SC-islet maturity by synchronizing circadian glucose-responsive insulin secretion rhythms and clock machinery. Thus, DEC1 links circadian control to human β-cell maturation, highlighting its vitality to foster fully functional SC-islets.

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