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Series GSE144955 Query DataSets for GSE144955
Status Public on Dec 03, 2020
Title Genome-wide mapping of 5-hydroxymethylcytosine enrichment in a novel model of 'NAFLD in a Dish'
Organism Homo sapiens
Experiment type Methylation profiling by high throughput sequencing
Summary Human pluriopotent H9 cells were differentiated to hepatocyte-like cells and exposed to a cocktail of lactate, pyruvate and octanoic acid (LPO) for 48 hours. This stimulated development of macrovesicular steatosis, which has previously been reported to impact on mitochondrial metabolism. Under our experimental conditions, we identified rewiring of the TCA cycle linked to macrovesicular steatosis. As key TCA cycle metabolites, alpha-ketoglutarate, succinate and fumarate impact on ten-eleven translocation (TET) enzyme activity, we hypothesised that this rewiring would impact on levels of 5-hydroxymethylcytosine (5hmC) enrichment across the genome. To this end, we performed DNA immunoprecipitation sequencing (DIPseq) to map any changes that occurred. Using IonTorrent, we sequenced our samples and generated bam files aligned to Homo sapiens Hg19. We used the MACS2 pipeline to compare our control and steatosis group, and identified a large number of changes in 5hmC enrichment in response to LPO exposure, indicating that TCA cycle wiring may impact on TET activity.
Overall design 5hmC profiles were generated for ES-derived hepatocyte-like cells following treatment with lactate (10 mM), pyruvate (1 mM) and octanoate (2 mM) to induce intracellular lipid accumulation, resulting in a NAFLD-like phenotype
Contributor(s) Drake AJ, Sinton MC
Citation(s) 33409477
Submission date Feb 07, 2020
Last update date Jan 09, 2021
Contact name Amanda J. Drake
Organization name University of Edinburgh
Department Centre for Cardiovascular Science
Street address 47 Little France Crescent
City Edinburgh
ZIP/Postal code EH16 4TJ
Country United Kingdom
Platforms (1)
GPL17303 Ion Torrent Proton (Homo sapiens)
Samples (9)
GSM4301418 Control 1
GSM4301419 Control 2
GSM4301420 Control 3
BioProject PRJNA605438
SRA SRP247654

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Supplementary file Size Download File type/resource
GSE144955_Differentially_bound_peaks_edgeR.csv.gz 321.1 Kb (ftp)(http) CSV
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