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Series GSE59091 Query DataSets for GSE59091
Status Public on Jan 27, 2016
Title Non-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells
Organism Homo sapiens
Experiment type Methylation profiling by genome tiling array
Summary Illumina Infinium 450k Human DNA Methylation BeadChip was used to obtain DNA methylation profiles across approximately 470,000 CpG and 2,700 non-CG loci in 195 DNA extracts from iPSCs, ESCs and donor cell lines.
Non-CG methylation is an unexplored epigenetic hallmark of pluripotent stem cells. Here we report that a reduction in non-CG methylation is associated with impaired differentiation capacity into endodermal lineages. Genome-wide analysis of 2,670 non-CG sites in a discovery cohort of 25 phenotyped human induced pluripotent stem cell (hiPSC) lines revealed unidirectional loss (Δβ = 13%, p<7.4x10-4) of non-CG methylation that correctly identifies endodermal differentiation capacity in 23 out of 25 (92%) hiPSC lines. Translation into a simplified assay of only 9 non-CG sites maintains predictive power in the discovery cohort (Δβ = 23%, p<9.1x10-6) and correctly identifies endodermal differentiation capacity in nince out of ten pluripotent stem cell lines in an independent replication cohort consisting of hiPSCs reprogrammed from different cell types and different delivery systems, as well as human embryonic stem cell (hESC) lines. This finding infers non-CG methylation at these sites as a biomarker when assessing endodermal differentiation capacity as a readout.
Overall design 25 iPSC lines, 3 ESC lines and 7 donor cell lines (samples) were represented by multiple DNA extracts (2 < N < 6); 7 iPSC line samples were represented by a single DNA extract. Each DNA extract was bisulphite converted and hybridised to the Illumina Infinium 450k Human Methylation BeadChip. Raw data was fed through the ChAMP analysis pipeline (Morris et al. 2013, Bioinformatics) and normalised using Subset-quantile Within Array Normalization (SWAN).
Contributor(s) Butcher LM
Citation(s) 26822956
Submission date Jul 03, 2014
Last update date Mar 22, 2019
Contact name Lee Butcher
Organization name University College London
Street address 72 Huntley Street
City London
ZIP/Postal code WC1E 6BT
Country United Kingdom
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (195)
GSM1427147 genomic DNA from DF-iPSC-230-79-R_1
GSM1427148 genomic DNA from DF-iPSC-230-79-R_2
GSM1427149 genomic DNA from DF-iPSC-230-79-R_3
BioProject PRJNA254466

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE59091_RAW.tar 183.1 Mb (http)(custom) TAR
GSE59091_unmethylated_methylated.txt.gz 439.2 Mb (ftp)(http) TXT
Processed data included within Sample table

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