Homo sapiens
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PROVIDER: PRJNA241240 | ENA |
REPOSITORIES: ENA
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Project description:Matrix Elasticity Does Not Affect Replicative Senescence or DNA Methylation Patterns of Mesenchymal Stem Cells [DNAm profiling]
| PRJNA241247 | ENA
Project description:Matrix elasticity influences differentiation of mesenchymal stem cells (MSCs) but it is unclear if these effects are only transient - while the cells reside on the substrate - or if they reflect persistent lineage commitment. In this study, MSCs were continuously culture-expanded in parallel either on polydimethylsiloxane (PDMS) gels of different elasticity or on tissue culture plastic (TCP) to compare impact on replicative senescence, in vitro differentiation, gene expression, and DNA methylation (DNAm) profiles. The maximal number of cumulative population doublings was not affected by matrix elasticity. Differentiation towards adipogenic and osteogenic lineage was increased on soft and rigid biomaterials, respectively - but this propensity was no more evident if cells were transferred to TCP. Global gene expression profiles and DNAm profiles revealed relatively few differences in MSCs cultured on soft or rigid matrices. Furthermore, only moderate DNAm changes were observed upon culture on very soft hydrogels of human platelet lysate (hPL-gel). Our results support the notion that matrix elasticity influences cellular differentiation while the cells are organized on the substrate, but it does not have major impact on cell-intrinsic lineage determination, replicative senescence or DNAm patterns. 20 samples were hybridized to the Illumina Infinium 450k Human Methylation Beadchip
2014-07-29 | E-GEOD-55888 | biostudies-arrayexpress
Project description:Matrix elasticity influences differentiation of mesenchymal stem cells (MSCs) but it is unclear if these effects are only transient - while the cells reside on the substrate - or if they reflect persistent lineage commitment. In this study, MSCs were continuously culture-expanded in parallel either on polydimethylsiloxane (PDMS) gels of different elasticity or on tissue culture plastic (TCP) to compare impact on replicative senescence, in vitro differentiation, gene expression, and DNA methylation (DNAm) profiles. The maximal number of cumulative population doublings was not affected by matrix elasticity. Differentiation towards adipogenic and osteogenic lineage was increased on soft and rigid biomaterials, respectively - but this propensity was no more evident if cells were transferred to TCP. Global gene expression profiles and DNAm profiles revealed relatively few differences in MSCs cultured on soft or rigid matrices. Furthermore, only moderate DNAm changes were observed upon culture on very soft hydrogels of human platelet lysate. Our results support the notion that matrix elasticity influences cellular differentiation while the cells are organized on the substrate, but it does not have major impact on cell-intrinsic lineage determination, replicative senescence or DNAm patterns. MSCs cultivated either on polydimethylsiloxane (PDMS) gels of different elasticity or on tissue culture plastic (TCP) to compare impact on gene expression profiles.
2014-07-29 | E-GEOD-55867 | biostudies-arrayexpress
Project description:Matrix elasticity influences differentiation of mesenchymal stem cells (MSCs) but it is unclear if these effects are only transient - while the cells reside on the substrate - or if they reflect persistent lineage commitment. In this study, MSCs were continuously culture-expanded in parallel either on polydimethylsiloxane (PDMS) gels of different elasticity or on tissue culture plastic (TCP) to compare impact on replicative senescence, in vitro differentiation, gene expression, and DNA methylation (DNAm) profiles. The maximal number of cumulative population doublings was not affected by matrix elasticity. Differentiation towards adipogenic and osteogenic lineage was increased on soft and rigid biomaterials, respectively - but this propensity was no more evident if cells were transferred to TCP. Global gene expression profiles and DNAm profiles revealed relatively few differences in MSCs cultured on soft or rigid matrices. Furthermore, only moderate DNAm changes were observed upon culture on very soft hydrogels of human platelet lysate (hPL-gel). Our results support the notion that matrix elasticity influences cellular differentiation while the cells are organized on the substrate, but it does not have major impact on cell-intrinsic lineage determination, replicative senescence or DNAm patterns.
2014-07-29 | GSE55888 | GEO
Project description:Matrix elasticity influences differentiation of mesenchymal stem cells (MSCs) but it is unclear if these effects are only transient - while the cells reside on the substrate - or if they reflect persistent lineage commitment. In this study, MSCs were continuously culture-expanded in parallel either on polydimethylsiloxane (PDMS) gels of different elasticity or on tissue culture plastic (TCP) to compare impact on replicative senescence, in vitro differentiation, gene expression, and DNA methylation (DNAm) profiles. The maximal number of cumulative population doublings was not affected by matrix elasticity. Differentiation towards adipogenic and osteogenic lineage was increased on soft and rigid biomaterials, respectively - but this propensity was no more evident if cells were transferred to TCP. Global gene expression profiles and DNAm profiles revealed relatively few differences in MSCs cultured on soft or rigid matrices. Furthermore, only moderate DNAm changes were observed upon culture on very soft hydrogels of human platelet lysate. Our results support the notion that matrix elasticity influences cellular differentiation while the cells are organized on the substrate, but it does not have major impact on cell-intrinsic lineage determination, replicative senescence or DNAm patterns.
2014-07-29 | GSE55867 | GEO
Project description:Pathogenic mutations in lamin A/C (LMNA) lead to nuclear structural abnormalities, mesenchymal tissue damage, and laminopathies, which have numerous tissue-specific and progeria phenotypes. However, how LMNA mutations lead to accelerated mesenchymal-derived cell senescence remains unclear. Here, we established a replicative senescence model in vitro using induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) from patients with homozygous LMNA p.R527C mutation (LMNA R527C iMSCs). R527C iMSCs exhibited marked cell senescence and stemness potential attenuation, accompanied by immunophenotypic changes when expanded to passage 13 in vitro. Proteome analysis revealed that DNA replication, nuclear structure, and chromatin-related gene sets were the most significant changes in R527C iMSCs during replicative senescence, and pathways such as cell cycle, DNA replication, cell adhesion, and inflammation might play important roles in senescence.
2022-10-21 | PXD037639 | iProX
Project description:Cells in culture undergo replicative senescence. In this study, we analyzed functional, genetic and epigenetic sequels of long‐term culture in human mesenchymal stem cells (MSC). Already within early passages the fibroblastoid colony‐ forming unit (CFU‐f) frequency and the differentiation potential of MSC declined significantly. Relevant chromosomal aberrations were not detected by karyotyping and SNP‐microarrays. Subsequently, we have compared DNA‐methylation profiles with the Infinium HumanMethylation27 Bead Array and the profiles differed markedly in MSC derived from adipose tissue and bone marrow. Notably, all MSC revealed highly consistent senescence‐associated modifications at specific CpG sites. These DNA‐methylation changes correlated with histone marks of previously published data sets, such as trimethylation of H3K9, H3K27 and EZH2 targets. Taken together, culture expansion of MSC has profound functional implications ‐ these are hardly reflected by genomic instability but they are associated with highly reproducible DNA‐methylation changes which correlate with repressive histone marks. Therefore replicative senescence seems to be epigenetically controlled. 8 samples of mesenchymal stem cells (MSC) from human adipose tissue
2011-10-27 | E-GEOD-26519 | biostudies-arrayexpress
Project description:The aim of the present study was to provide a comprehensive characterization of whole genome DNA methylation patterns in replicative and ionizing irradiation- or doxorubicin-induced premature senescence, exhaustively exploring epigenetic modifications in three different human cell types: in somatic diploid skin fibroblasts and in bone marrow- and adipose-derived mesenchymal stem cells. With CpG-wise differential analysis three epigenetic signatures were identified: a) cell type- and treatment-specific signature; b) cell type-specific senescence-related signature; and c) cell type-transversal replicative senescence-related signature. Cluster analysis revealed that only replicatively senescent cells created a distinct group reflecting notable alterations in the DNA methylation patterns accompanying this cellular state. Replicative senescence-associated epigenetic changes seemed to be of such an extent that they surpassed interpersonal dissimilarities. Enrichment in pathways linked to the nervous system and involved in the neurological functions was shown after pathway analysis of genes involved in the cell type-transversal replicative senescence-related signature. Although DNA methylation clock analysis provided no statistically significant evidence on epigenetic age acceleration related to senescence, a persistent trend of increased biological age in replicatively senescent cultures of all three cell types was observed. Overall, this work indicates the heterogeneity of senescent cells depending on the tissue of origin and the type of senescence inducer that could be putatively translated to a distinct impact on tissue homeostasis.
2023-03-20 | GSE227160 | GEO
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 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
2012-09-24 | E-GEOD-37066 | biostudies-arrayexpress