Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pluripotent Stem Cells Escape From Senescence-Associated DNA Methylation Changes [Illumina]

ABSTRACT: Pluripotent stem cells evade replicative senescence, whereas other primary cells lose their proliferation and differentiation potential after a limited number of cell divisions M-bM-^@M-^S and this is accompanied by specific senescence-associated DNA methylation (SA-DNAm) changes. Here, we investigate SA-DNAm changes in mesenchymal stromal cells (MSC) upon long-term culture, irradiation-induced senescence, immortalization and reprogramming into induced pluripotent stem cells (iPSC) using high density HumanMethylation450 BeadChips. SA-DNAm changes are highly reproducible and occur particularly in intergenic and non-promoter regions of developmental genes. We demonstrate that ionizing irradiation, although associated with a very similar senescence phenotype, does not affect SA-DNAm. Furthermore, overexpression of the catalytic subunit of the human telomerase (TERT) or conditional immortalization with a doxycycline-inducible system (TERT and SV40 TAg) result in telomere extension but do not influence SA-DNAm. In contrast, we demonstrate that reprogramming into iPSC prevented SA-DNAm changes. Our results indicate that replicative senescence is associated with an epigenetically controlled process which stalls cells in a particular differentiated state, whereas irradiation-induced senescence and immortalization are not causally related to this process. Absence of SA-DNAm in pluripotent cells may play a central role for their escape from cellular senescence. Samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

ORGANISM(S): Homo sapiens

SUBMITTER: Wolfgang Wagner

PROVIDER: E-GEOD-37066 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Pluripotent Stem Cells Escape From Senescence-Associated DNA Methylation Changes

Project description:This SuperSeries is composed of the following subset Series: GSE37065: Long-term culture associated gene expression changes in MSC [Affymetrix] GSE37066: Pluripotent Stem Cells Escape From Senescence-Associated DNA Methylation Changes [Illumina] GSE38806: Gene expression profiles of induced pluripotent mesenchymal stromal cells [Affymetrix] Refer to individual Series

2012-09-24 | E-GEOD-37067 | biostudies-arrayexpress

Pluripotent Stem Cells Escape From Senescence-Associated DNA Methylation Changes [Illumina]

Project description:Pluripotent stem cells evade replicative senescence, whereas other primary cells lose their proliferation and differentiation potential after a limited number of cell divisions – and this is accompanied by specific senescence-associated DNA methylation (SA-DNAm) changes. Here, we investigate SA-DNAm changes in mesenchymal stromal cells (MSC) upon long-term culture, irradiation-induced senescence, immortalization and reprogramming into induced pluripotent stem cells (iPSC) using high density HumanMethylation450 BeadChips. SA-DNAm changes are highly reproducible and occur particularly in intergenic and non-promoter regions of developmental genes. We demonstrate that ionizing irradiation, although associated with a very similar senescence phenotype, does not affect SA-DNAm. Furthermore, overexpression of the catalytic subunit of the human telomerase (TERT) or conditional immortalization with a doxycycline-inducible system (TERT and SV40 TAg) result in telomere extension but do not influence SA-DNAm. In contrast, we demonstrate that reprogramming into iPSC prevented SA-DNAm changes. Our results indicate that replicative senescence is associated with an epigenetically controlled process which stalls cells in a particular differentiated state, whereas irradiation-induced senescence and immortalization are not causally related to this process. Absence of SA-DNAm in pluripotent cells may play a central role for their escape from cellular senescence.

2012-09-24 | GSE37066 | GEO

Long-term culture associated gene expression changes in MSC [Affymetrix]

Project description:Mesenchymal stromal cells (MSC) were isolated from human bone marrow. Here, we have compared gene expression profiles of MSC at early and late passages. Long-term culture associated gene expression changes were then correlated with DNA-methylation profiles. The goal of this study was to determine if senescence-associated DNA-methylation (SA-DNAm) changes are reflected by differential gene expression. Overall, genes with SA-DNAm changes (particularly with SA-hypomethylation) were detected at low level and seemed to be scarcely expressed at early and late passages. MSC were isolated from three different donors and culture expanded until replicative senescence. Gene expression profiles were compared at early and late passage using GeneChip Humang Gene 1.0 ST arrays (Affymetrix). Six hybridizations are included in this series.

2012-09-24 | E-GEOD-37065 | biostudies-arrayexpress

Tissue- and Aging-specific DNA-Methylation Patterns are erased in Mesenchymal Stromal Cells derived from Induced Pluripotent Stem Cells. [Expression profiling]

Project description:Standardization of mesenchymal stromal cells (MSCs) remains a major obstacle in regenerative medicine. Starting material and culture expansion affect cell preparations and render comparison between studies difficult. In contrast, induced pluripotent stem cells (iPSCs) assimilate towards a ground-state and may therefore give rise to more standardized cell preparations. We reprogrammed bone marrow MSCs into iPSCs which were subsequently re-differentiated towards MSCs. These iPS-MSCs revealed similar morphology, immunophenotype, in vitro differentiation potential, and gene expression profiles as primary MSCs. DNA methylation (DNAm) profiles of iPSCs maintained some donor-specific characteristics, whereas tissue-specific, senescence-associated, and age-related DNAm patterns were erased during reprogramming. iPS-MSCs reacquired senescence-associated DNAm during culture expansion but they remained rejuvenated with regard to age-related DNAm. Overall, iPS-MSCs and MSCs are similar in function but differ in their epigenetic makeup. 8 samples were hybridized to the GeneChip Human Gene 1.0 ST Array (Affymetrix)

2014-09-24 | E-GEOD-54766 | biostudies-arrayexpress

Tissue- and Aging-specific DNA-Methylation Patterns are erased in Mesenchymal Stromal Cells derived from Induced Pluripotent Stem Cells. [Methylation profiling]

Project description:Standardization of mesenchymal stromal cells (MSCs) remains a major obstacle in regenerative medicine. Starting material and culture expansion affect cell preparations and render comparison between studies difficult. In contrast, induced pluripotent stem cells (iPSCs) assimilate towards a ground-state and may therefore give rise to more standardized cell preparations. We reprogrammed bone marrow MSCs into iPSCs which were subsequently re-differentiated towards MSCs. These iPS-MSCs revealed similar morphology, immunophenotype, in vitro differentiation potential, and gene expression profiles as primary MSCs. DNA methylation (DNAm) profiles of iPSCs maintained some donor-specific characteristics, whereas tissue-specific, senescence-associated, and age-related DNAm patterns were erased during reprogramming. iPS-MSCs reacquired senescence-associated DNAm during culture expansion but they remained rejuvenated with regard to age-related DNAm. Overall, iPS-MSCs and MSCs are similar in function but differ in their epigenetic makeup. 12 samples were hybridized to the Illumina Infinium 450k Human Methylation Beadchip

2014-09-24 | E-GEOD-54767 | biostudies-arrayexpress

Replicative senescence is associated with nuclear reorganization and DNA methylation at specific transcription factor binding sites (MBD-seq)

Project description:Primary cells enter replicative senescence after a limited number of cell divisions. This process is associated with reproducible changes in DNA methylation (DNAm) at specific sites in the genome. The mechanism that drives senescence-associated DNAm changes remains unknown and may arise through drift in DNAm or through regulated, senescence dependent modifications at specific sites in the genome. In this study, we analyzed the reorganization of nuclear architecture and DNA methylation during long-term culture of human fibroblasts and mesenchymal stromal cells (MSCs). [MethylCap-seq] Fibroblasts of two female donors (both 43 years old) were culture expanded and DNA was harvested of 10,000,000 cells at early passage (P3 or P5) and late passage (P30 and P33). DNA methylation changes were subsequently analyzed by MethylCap-Seq.

2015-03-26 | E-GEOD-59960 | biostudies-arrayexpress

Replicative senescence is associated with nuclear reorganization and DNA methylation at specific transcription factor binding sites (RNA-seq)

Project description:Primary cells enter replicative senescence after a limited number of cell divisions. This process is associated with reproducible changes in DNA methylation (DNAm) at specific sites in the genome. The mechanism that drives senescence-associated DNAm changes remains unknown and may arise through drift in DNAm or through regulated, senescence dependent modifications at specific sites in the genome. In this study, we analyzed the reorganization of nuclear architecture and DNA methylation during long-term culture of human fibroblasts and mesenchymal stromal cells (MSCs). [RNA-seq] RNA was isolated from 1,000,000 cells of three MSC donors (59, 64, and 73 years old) at passage 4 and passage 13 using the miRNeasy Mini Kit (Qiagen). Gene expression profiles were analzyed by deep sequencing with IlluminaHiSeq 2000 technology with a read length of 50 bases at EMBL gene core facility (Heidelberg, Germany).

2015-03-26 | E-GEOD-59966 | biostudies-arrayexpress

Long-term culture associated gene expression changes in MSC [Affymetrix]

2012-09-24 | GSE37065 | GEO

Induced Pluripotent Mesenchymal Stromal Cell Clones Retain Donor-Derived Differences in DNA Methylation Profiles

Project description: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. 16 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

2013-01-09 | E-GEOD-34688 | biostudies-arrayexpress

Effects of Cellular Senescence on Human Mesenchymal Stem Cells

Project description:In the present study we analyzed the effect of cellular senescence on the transcriptome of human mesenchymal stem cells (hMSC; alternatively named mesenchymal stromal cells) from bone marrow. Human MSC were isolated from femoral heads of non-osteoporotic donors after total hip arthroplasty. Cells were isolated from human bone marrow according to the previously described protocol (Noth et al., 2002, J Orthop Res, 20/5, 1060-1069) under agreement of the local Ethics Committee of the University of Würzburg. Bone marrow was obtained of femoral heads after total hip arthroplasty due to osteoarthritis and/or hip dysplasia. MSC were replated after reaching 70-90% confluence until they entered state of cellular senescence. RNA samples of control cells were taken from passage 1 or passage 2.

2012-02-22 | E-GEOD-35957 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data