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| Status |
Public on Jan 09, 2013 |
| Title |
Induced Pluripotent Mesenchymal Stromal Cell Clones Retain Donor-Derived Differences in DNA Methylation Profiles |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
Reprogramming of somatic cells into induced pluripotent stem cells (iPSC) is an epigenetic phenomenon. It has been suggested that iPSC retain some tissue-specific memory whereas little is known about inter-individual epigenetic variation of iPSC clones. In this study we have reprogrammed mesenchymal stromal cells (MSC) from human bone marrow by retrovirus-mediated overexpression of OCT-3/4, SOX2, c-MYC, and KLF4. Global DNA-methylation profiles of the initial MSC, MSC-derived iPSC (iP-MSC) and embryonic stem cells (ESC) were then compared using a high density DNA-methylation array covering more than 450,000 CpG sites. Overall, DNA-methylation patterns of iP-MSC and ESC were similar whereas some CpG sites revealed highly significant differences, which were not related to parental MSC. Furthermore, hypermethylation in iP-MSC versus ESC was particularly enriched in developmental genes as well as shore regions next to CpG islands indicating that these differences are not due to tissue-specific memory or random de novo methylation. Subsequently, we searched for CpG sites with donor-specific variation in MSC preparations. These “epigenetic fingerprints” were highly enriched in non-promoter regions and outside of CpG islands – and they were maintained upon reprogramming into iP-MSC. In conclusion, DNA methylation profiles of iP-MSC clones from the same donor were closely related despite heterogeneity of MSC. On the other hand, iP-MSC maintain donor-derived epigenetic differences. In the absence of isogenic controls for disease modeling applications, it would therefore be more appropriate to compare iPSC from different donors rather than a high number of different clones from the same patient.
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| Overall design |
16 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
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| Contributor(s) |
Shao K, Koch C, Gupta MK, Lin Q, Lenz M, Laufs S, Denecke B, Schmidt M, Linke M, Hennies HC, Hescheler J, Zechner U, Saric T, Wagner W |
| Citation(s) |
23032973, 25241740 |
| Submission date |
Dec 23, 2011 |
| Last update date |
Mar 22, 2019 |
| Contact name |
Wolfgang Wagner |
| E-mail(s) |
wwagner@ukaachen.de
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| Phone |
+49 241 8088611
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| Organization name |
RWTH Aachen University
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| Department |
Helmholtz Institute for Biomedical Engineering
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| Lab |
Stem Cell Biology and Cellular Engineering
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| Street address |
Pauwelsstrasse 20
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| City |
Aachen |
| ZIP/Postal code |
52074 |
| Country |
Germany |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA150297 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE34688_Matrix_signals_GSM853409-GSM853422.txt.gz |
42.5 Mb |
(ftp)(http) |
TXT |
| GSE34688_Matrix_signals_GSM979892-GSM979893.txt.gz |
9.9 Mb |
(ftp)(http) |
TXT |
| GSE34688_RAW.tar |
183.1 Mb |
(http)(custom) |
TAR |
| Processed data included within Sample table |
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