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Chromatin dynamics reveal circadian control of human in vitro islet maturation

ABSTRACT: Chromatin dynamics reveal circadian control of human in vitro islet maturation

PROVIDER: PRJNA587096 | ENA |

REPOSITORIES: ENA

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Chromatin dynamics reveal circadian control of human in vitro islet maturation [WGBS]

Project description:Stem cell-derived tissues could transform disease research and therapy, yet most methods generate functionally immature products. We investigate how human stem cells differentiate into pancreatic islets in vitro by profiling DNA methylation, chromatin accessibility, and histone modification changes. We find that enhancer potential is reset upon lineage commitment, and show how pervasive epigenetic priming steers endocrine cell fates. Modeling islet differentiation and maturation regulatory circuits reveals genes critical for generating endocrine cells and identifies circadian control as limiting for in vitro islet function. Entrainment to circadian feeding/fasting cycles triggers islet metabolic maturation by inducing cyclic synthesis of energy metabolism and insulin secretion effectors, including antiphasic insulin and glucagon pulses. Following entrainment, stem cell-derived islets gain persistent chromatin changes and rhythmic insulin responses with a raised glucose threshold, a hallmark of functional maturity, and function within days of transplantation. Thus, stem cell-derived tissues are amenable to functional improvement by circadian modulation.

2019-11-16 | GSE140501 | GEO

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

2019-11-16 | GSE140500 | GEO

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

2019-11-16 | GSE140499 | GEO

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

2019-11-02 | GSE139816 | GEO

Chromatin dynamics reveal circadian control of human in vitro islet maturation [WGBS]

Project description:Chromatin dynamics reveal circadian control of human in vitro islet maturation [WGBS]

| PRJNA589906 | ENA

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

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

| PRJNA587101 | ENA

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

Project description:Chromatin dynamics reveal circadian control of human in vitro islet maturation [ChIP-seq]

| PRJNA589907 | ENA

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

Project description:Chromatin dynamics reveal circadian control of human in vitro islet maturation [ATAC-seq]

| PRJNA589908 | ENA

Chromatin dynamics reveal circadian control of human in vitro islet maturation

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-11-02 | GSE139817 | GEO

Islet-specific microRNA changes driven by nutrient shift trigger postnatal beta-cell maturation - intact islet microRNAs

Project description:We found that in rodents, postnatal beta-cell maturation is associated with changes in the expression of several islet microRNAs and discovered that these modifications are driven by changes in the nutrient supply. Mimicking the microRNA changes observed during ?-cell maturation in newborn rat islet cells was sufficient to promote glucose-induced insulin release and to achieve a mature ?-cell secretory phenotype. Moreover, the modifications in the level of some of these microRNAs reduced the proliferation of newborn ?-cells, suggesting that they contribute to the limited proliferative capacity of adult ?-cells. These findings demonstrated that miRNAs contribute to postnatal beta-cell maturation and development. Their role is likely to promote beta-cell adaptation to fule supply and to maintain glucose homeostasis by regulating insulin release and proliferation. Islets from 10-day-old rats (P10) (n=5) or 3-month-old male rat (n=6) were taken. Total RNA was extracted and microRNA profiling was performed using the Illumina TruSeq small RNA kit and single-end sequencing.

2014-09-06 | E-GEOD-61180 | biostudies-arrayexpress

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