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Series GSE54848 Query DataSets for GSE54848
Status Public on Aug 04, 2014
Title Critical role of transient activation of human endogenous retroviruses during reprogramming toward pluripotency
Organism Homo sapiens
Experiment type Expression profiling by array
Methylation profiling by array
Summary We recently showed that some human induced pluripotent stem cell (iPSC) clones were defective in neural differentiation and were marked with the activation of long term repeats (LTRs) of human endogenous retroviruses (HERVs). We herein demonstrated that these LTRs were transiently overexpressed during the generation of iPSCs and contributed to reprogramming. When the generation of iPSCs was completed, LTRs were re-suppressed to levels similar to those in human ES cells. However, differentiation-defective iPSC clones maintained high LTR expression levels, which indicated that these clones failed to complete reprogramming. lincRNA-RoR, a long intergenic non-coding RNA (lincRNA) that was previously shown to support the induction and maintenance of pluripotency, was detected among the LTR-driven transcripts. Short hairpin RNAs against the conserved sequence in LTRs or lincRNA-RoR markedly reduced the efficiency of iPSC generation. Reprogramming factors including OCT3/4, SOX2, and KLF4 bound to most LTRs. The expression of KLF4 was low in normal iPSC clones, but remained high in differentiation-defective clones. The forced expression of KLF4 in human embryonic stem cells led to the activation of LTRs and defects in neural differentiation. These results demonstrated that the transient overexpression of KLF4/LTR/lincRNA-RoR played crucial roles in reprogramming toward pluripotency in humans, whereas a failure in its re-silence resulted in differentiation defects.
 
Overall design Four human induced pluripotent stem cell lines were subcloned into 55 separate lines. Bisulfite converted genomic DNA lysates from fibroblast, induced pluripotent stem cell, intermediate reprogrammed cell and embryonic stem cell lines were hybridized to Illumina HumanMethylation450 BeadChip.
 
Contributor(s) Ohnuki M, Yamanaka S, Takahashi K
Citation(s) 25097266
Submission date Feb 10, 2014
Last update date Mar 22, 2019
Contact name Kazutoshi Takahashi
E-mail takahash@cira.kyoto-u.ac.jp
Organization name Kyoto University
Department Center for iPS Cell Research and Application
Street address 53 Kawahara-cho, Shogoin, Sakyo-ku
City Kyoto
ZIP/Postal code 606-8507
Country Japan
 
Platforms (2)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
GPL14550 Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Probe Name Version)
Samples (137)
GSM1325080 451F3s1
GSM1325081 451F3s2
GSM1325082 451F3s3
Relations
BioProject PRJNA237810

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE54848_RAW.tar 515.7 Mb (http)(custom) TAR (of TXT)
GSE54848_signal_intensities.txt.gz 68.3 Mb (ftp)(http) TXT
Raw data provided as supplementary file
Processed data included within Sample table
Raw data is available on Series record

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