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Series GSE59696 Query DataSets for GSE59696
Status Public on Jul 30, 2014
Title The developmental potential of iPSCs is greatly influenced by the selection of the reprogramming factors
Organism Mus musculus
Experiment type Methylation profiling by high throughput sequencing
Summary Induced pluripotent stem cells (iPSCs) are commonly generated by transduction of Oct4, Sox2, Klf4 and Myc (OSKM) into somatic cells. Though iPSCs are pluripotent, they frequently exhibit high variation in their quality as measured by chimera contribution and tetraploid (4n) complementation. Thus, improving the quality of iPSCs is an indispensable prerequisite for future iPSC-based therapy. Here we show that one major determinant for iPSCs quality is the combination of reprograming factor selected. Ectopic expression of Sall4, Nanog, Esrrb and Lin28 (SNEL) in MEFs efficiently generated high quality iPSCs as compared to other combinations of factors. SNEL-iPSCs produced approximately 5 times more efficiently “all-iPSC” mice compared to OSKM-iPSCs. While differentially methylated regions, transcript number of master regulators, establishment of ESC-specific super enhancers, and global aneuploidy were comparable between the lines, aberrant expression of 1,765 genes, trisomy of chromosome 8 and abnormal H2A.X deposition were frequently observed in poor quality OSK-iPSCs and OSKM-iPSCs.
Overall design Whole-genome single-base resolution MethylC sequencing collected from a variety of Mouse pluripotent cells
To reveal the DNA methylation signature associated with developmental competence, we selected the following groups of iPSC lines for whole-genome bisulfite sequencing:
i) "Poor quality" iPSCs: This group included the three OSKM-iPSC lines Nanog-GFP OSKM#2, Oct4-GFP OSKM#2 and KH2 OSKM(Stadtfeld et al., 2010), that either did not produce fully developed pups or produced very low number of pups;
ii) "Good quality" iPSCs: This group included BC_2 OSKM (Carey et al., 2011) and Nanog-GFP SNEL#3, both of which gave rise to live, normal pups that survived only few hours;
iii) "High quality" iPSCs consisting of Nanog-GFP SNEL#2 and Oct4-GFP SNEL#1, both of which generated live pups that survived postnatally (representative pups from each iPSC group are shown in Figure S3A).
iv) As controls we used Nanog-GFP, Oct4-GFP and KH2 (Beard et al., 2006) ESCs. Note that all cells were cultured in 2i medium but not in mES medium.
Contributor(s) He Y, Schultz MD, Nery JR, Ecker JR
Citation(s) 25192464
Submission date Jul 23, 2014
Last update date May 15, 2019
Contact name Joseph R Ecker
Phone 8584534100
Organization name HHMI-Salk-Institute
Department Genomic Analysis Laboratory
Lab Ecker lab
Street address 10010 North Torrey Pines Road
City La Jolla
State/province CA
ZIP/Postal code 92037
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (10)
GSM1448286 BC_2 OKSM
GSM1448287 KH2 OKSM
GSM1448288 KH2 ESC
BioProject PRJNA256919
SRA SRP045054

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Supplementary file Size Download File type/resource
GSE59696_RAW.tar 37.4 Gb (http)(custom) TAR (of TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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