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Series GSE140499 Query DataSets for GSE140499
Status Public on Nov 16, 2019
Title Chromatin dynamics reveal circadian control of human in vitro islet maturation [ATAC-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary 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.
Overall design ATAC-sequencing of purified live cells at defined developmental stages from stem cells to mature pancreatic islet α/β cells
ATAC-sequencing of purified live cells differentiated from human pluripotent stem cells from Stage 6 week 0 to Stage 6 week 4.
Contributor(s) Alvarez-Dominguez JR
Citation(s) 31839570
Submission date Nov 15, 2019
Last update date Feb 04, 2020
Contact name Juan R Alvarez-Dominguez
Organization name Harvard University
Department Stem Cell and Regenerative Biology
Street address 7 Divinity Ave
City Cambridge
State/province MA
ZIP/Postal code 02138
Country USA
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (39)
GSM4171636 PP2_ATAC_rep1
GSM4171637 EN_ATAC_rep1
GSM4171638 SCbeta_ATAC_rep1
This SubSeries is part of SuperSeries:
GSE139817 Chromatin dynamics reveal circadian control of human in vitro islet maturation
BioProject PRJNA589908
SRA SRP230219

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Supplementary file Size Download File type/resource
GSE140499_RAW.tar 31.2 Mb (http)(custom) TAR (of BED, TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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