The Senescent Methylome and its relationship with cancer, ageing, and germline genetic variation in humans
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE58035 | GEO | 2015/07/24
SECONDARY ACCESSION(S): PRJNA248738
REPOSITORIES: GEO
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-07-24 | E-GEOD-58035 | biostudies-arrayexpress
Project description:Cellular senescence is a stable arrest of proliferation and is considered a key component of processes associated with carcinogenesis and other ageing-related phenotypes. Here, we perform methylome analysis of actively dividing and deeply senescent normal human epithelial cells.We identify senescence-associated differentially methylated positions (senDMPs) from multiple experiments using cells from one donor. We find that human senDMP epigenetic signatures are positively and significantly correlated with both cancer and ageing-associated methylation dynamics. We also identify germline genetic variants, including those associated with the p16INK4A locus, which are associated with the presence of in vivo senDMP signatures. Importantly, we also demonstrate that a single senDMP signature can be effectively reversed in a newly-developed protocol of transient senescence reversal.The senDMP signature has significant potential for understanding some of the key (epi)genetic etiological factors that may lead to cancer and age-related diseases in humans.
| S-EPMC4574115 | biostudies-other
Project description:Cellular senescence is a stable arrest of proliferation and is considered a key component of processes associated with carcinogenesis and other ageing-related phenotypes. However, till now, biological markers that define senescence on a genome-wide scale have been limited. Here, we report a DNA methylomic analysis of actively dividing and deeply senescent normal human epithelial cells, identifying 3,852 senescence-associated differentially methylated positions (senDMPs). We find that this human senDMP signature is positively and significantly correlated with both cancer and ageing-associated methylomic dynamics. We also identify germline genetic variants, including those associated with the p16INK4A locus, that are associated with the presence of in vivo senDMP signatures. Importantly, we also demonstrate that the senDMP signature can be effectively reversed in a newly-developed protocol of transient cellular rejuvenation. The senDMP signature has significant potential for understanding some of the key (epi)genetic etiological factors that lead to cancer and age-related diseases in humans. Total RNA obtained from the HMECs at early passage (EP) and deep senescence (DS)
2015-07-26 | E-GEOD-56718 | biostudies-arrayexpress
Project description:Cellular senescence is a stable arrest of proliferation and is considered a key component of processes associated with carcinogenesis and other ageing-related phenotypes. However, till now, biological markers that define senescence on a genome-wide scale have been limited. Here, we report a DNA methylomic analysis of actively dividing and deeply senescent normal human epithelial cells, identifying 3,852 senescence-associated differentially methylated positions (senDMPs). We find that this human senDMP signature is positively and significantly correlated with both cancer and ageing-associated methylomic dynamics. We also identify germline genetic variants, including those associated with the p16INK4A locus, that are associated with the presence of in vivo senDMP signatures. Importantly, we also demonstrate that the senDMP signature can be effectively reversed in a newly-developed protocol of transient cellular rejuvenation. The senDMP signature has significant potential for understanding some of the key (epi)genetic etiological factors that lead to cancer and age-related diseases in humans.
2015-07-26 | GSE56718 | GEO
Project description:Cellular senescence is a stable arrest of proliferation and is considered a key component of processes associated with carcinogenesis and other ageing-related phenotypes. However, till now, biological markers that define senescence on a genome-wide scale have been limited. Here, we report a DNA methylomic analysis of actively dividing and deeply senescent normal human epithelial cells, identifying 3,852 senescence-associated differentially methylated positions (senDMPs). We find that this human senDMP signature is positively and significantly correlated with both cancer and ageing-associated methylomic dynamics. We also identify germline genetic variants, including those associated with the p16INK4A locus, that are associated with the presence of in vivo senDMP signatures. Importantly, we also demonstrate that the senDMP signature can be effectively reversed in a newly-developed protocol of transient cellular rejuvenation. The senDMP signature has significant potential for understanding some of the key (epi)genetic etiological factors that lead to cancer and age-related diseases in humans. Bisulphite converted DNA from the HMECs at early passage (EP), deep senescence (DS), deep senescence + p16 siRNA (DS+p16siRNA) at two different time points and FACS for cell cycle at EP were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
2015-07-26 | E-GEOD-69046 | biostudies-arrayexpress
Project description:Cellular senescence is a stable arrest of proliferation and is considered a key component of processes associated with carcinogenesis and other ageing-related phenotypes. However, till now, biological markers that define senescence on a genome-wide scale have been limited. Here, we report a DNA methylomic analysis of actively dividing and deeply senescent normal human epithelial cells, identifying 3,852 senescence-associated differentially methylated positions (senDMPs). We find that this human senDMP signature is positively and significantly correlated with both cancer and ageing-associated methylomic dynamics. We also identify germline genetic variants, including those associated with the p16INK4A locus, that are associated with the presence of in vivo senDMP signatures. Importantly, we also demonstrate that the senDMP signature can be effectively reversed in a newly-developed protocol of transient cellular rejuvenation. The senDMP signature has significant potential for understanding some of the key (epi)genetic etiological factors that lead to cancer and age-related diseases in humans. Bisulphite converted DNA from the HMECs at early passage (EP), deep senescence (DS), deep senescence + p16 siRNA (DS+p16siRNA) at two different time points and FACS for cell cycle at EP were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
2015-07-26 | E-GEOD-56719 | biostudies-arrayexpress
Project description:Cellular senescence is a stable arrest of proliferation and is considered a key component of processes associated with carcinogenesis and other ageing-related phenotypes. However, till now, biological markers that define senescence on a genome-wide scale have been limited. Here, we report a DNA methylomic analysis of actively dividing and deeply senescent normal human epithelial cells, identifying 3,852 senescence-associated differentially methylated positions (senDMPs). We find that this human senDMP signature is positively and significantly correlated with both cancer and ageing-associated methylomic dynamics. We also identify germline genetic variants, including those associated with the p16INK4A locus, that are associated with the presence of in vivo senDMP signatures. Importantly, we also demonstrate that the senDMP signature can be effectively reversed in a newly-developed protocol of transient cellular rejuvenation. The senDMP signature has significant potential for understanding some of the key (epi)genetic etiological factors that lead to cancer and age-related diseases in humans.
2015-07-26 | GSE69046 | GEO
Project description:Cellular senescence is a stable arrest of proliferation and is considered a key component of processes associated with carcinogenesis and other ageing-related phenotypes. However, till now, biological markers that define senescence on a genome-wide scale have been limited. Here, we report a DNA methylomic analysis of actively dividing and deeply senescent normal human epithelial cells, identifying 3,852 senescence-associated differentially methylated positions (senDMPs). We find that this human senDMP signature is positively and significantly correlated with both cancer and ageing-associated methylomic dynamics. We also identify germline genetic variants, including those associated with the p16INK4A locus, that are associated with the presence of in vivo senDMP signatures. Importantly, we also demonstrate that the senDMP signature can be effectively reversed in a newly-developed protocol of transient cellular rejuvenation. The senDMP signature has significant potential for understanding some of the key (epi)genetic etiological factors that lead to cancer and age-related diseases in humans.
2015-07-26 | GSE56719 | GEO
Project description:Senescence, a state of permanent cell cycle arrest, can be induced by DNA damage. This process, which was initially described in fibroblasts, is now recognized to occur in stem cells. It has been well characterized in cell lines, but there is currently very limited data available on human senescence in vivo. We recently reported that the expression of transposable elements (TE), including endogenous retroviruses, was up-regulated along with inflammatory genes in human senescent hematopoietic stem and progenitor cells (HSPCs) in vivo. The mechanism of regulation of TE expression is not completely understood, but changes in DNA methylation and chromatin modifications are known to alter their expression. In order to elucidate the molecular mechanisms for TE up-regulation after senescence of HSPCs, we employed whole-genome bisulfite sequencing in paired senescent and active human HSPCs in vivo from healthy subjects. We found that the senescent HSPCs exhibited hypomethylated regions in the genome, which were enriched for TEs. This is the first report characterizing the methylome of senescent human HSPCs.
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-12-13 | E-GEOD-53261 | biostudies-arrayexpress