Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA139059 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Gene expression profile of p53 knockdown MSCs or p53 knockdown+TERT MSCs was compared with that of control MSCs. Our data show p53 knockdown prolongs the lifespan of MSCs, and a combination of p53 knockdown and TERT overexpression is sufficient to immortalize MSCs. The results provide important information about the molecular basis underlying p53 knockdown in MSCs and immortalization-related genes of MSCs. Total RNA obtained from p53 knockdown MSCs or p53 knockdown+TERT MSCs from three patients were compared with control MSCs.
2011-04-13 | E-GEOD-28546 | biostudies-arrayexpress
Project description:Gene expression profile of p53 knockdown MSCs or p53 knockdown+TERT MSCs was compared with that of control MSCs. Our data show p53 knockdown prolongs the lifespan of MSCs, and a combination of p53 knockdown and TERT overexpression is sufficient to immortalize MSCs. The results provide important information about the molecular basis underlying p53 knockdown in MSCs and immortalization-related genes of MSCs.
2011-04-13 | GSE28546 | GEO
Project description:The secretome of mesenchymal stromal cells (MSCs) can efficiently stimulate regener-ation and therefore is a tempting remedy for “cell-free cellular therapy”. However, the usage of primary MSC cultures as secretome-producers for translation studies has ob-vious obstacles, including rapid aging of MSC cultures, the need for a large number of verified donors and donor-to-donor variability of secretome content. MSCs immortal-ization allows to overcome those limitations and to obtain secretome-producing cul-tures with prolonged lifetime. However, the efficacy and safety of such secretomes are critical issues, which limit their usage as therapeutic agents. In this study we have tested in large detail how the immortalization of MSC cultures affects the content, bi-ological activity and safety of their secretome. MSCs immortalization via overexpres-sion of human TERT gene does not significantly alter the qualitative and quantitative composition of their secretome or its activity according to the results of proteomic analysis, ELISA, qPCR and functional tests in vitro. Moreover, we have demonstrated that the secretome of immortalized MSCs does not contain detectable amounts of te-lomerase and does not possess any transforming activity. Altogether, our data suggest that immortalized MSC cultures may become a reliable source for obtaining standard-ized active secretome in large-scale quantities for clinical use.The secretome of mesenchymal stromal cells (MSCs) can efficiently stimulate regener-ation and therefore is a tempting remedy for “cell-free cellular therapy”. However, the usage of primary MSC cultures as secretome-producers for translation studies has ob-vious obstacles, including rapid aging of MSC cultures, the need for a large number of verified donors and donor-to-donor variability of secretome content. MSCs immortal-ization allows to overcome those limitations and to obtain secretome-producing cul-tures with prolonged lifetime. However, the efficacy and safety of such secretomes are critical issues, which limit their usage as therapeutic agents. In this study we have tested in large detail how the immortalization of MSC cultures affects the content, bi-ological activity and safety of their secretome. MSCs immortalization via overexpres-sion of human TERT gene does not significantly alter the qualitative and quantitative composition of their secretome or its activity according to the results of proteomic analysis, ELISA, qPCR and functional tests in vitro. Moreover, we have demonstrated that the secretome of immortalized MSCs does not contain detectable amounts of te-lomerase and does not possess any transforming activity. Altogether, our data suggest that immortalized MSC cultures may become a reliable source for obtaining standard-ized active secretome in large-scale quantities for clinical use.
2025-10-27 | PXD067843 | Pride
Project description:The secretome of mesenchymal stromal cells (MSCs) can efficiently stimulate regeneration and therefore is a tempting remedy for “cell-free cellular therapy”. However, the usage of primary MSC cultures as secretome-producers for translation studies has obvious obstacles, including rapid aging of MSC cultures, the need for a large number of verified donors and donor-to-donor variability of secretome content. MSCs immortalization allows to overcome those limitations and to obtain secretome-producing cultures with prolonged lifetime. However, the efficacy and safety of such secretomes are critical issues, which limit their usage as therapeutic agents. In this study we have tested in large detail how the immortalization of MSC cultures affects the content, biological activity and safety of their secretome. MSCs immortalization via overexpression of human TERT gene does not significantly alter the qualitative and quantitative composition of their secretome or its activity according to the results of proteomic analysis, ELISA, qPCR and functional tests in vitro. Moreover, we have demonstrated that the secretome of immortalized MSCs does not contain detectable amounts of telomerase and does not possess any transforming activity. Altogether, our data suggest that immortalized MSC cultures may become a reliable source for obtaining standardized active secretome in large-scale quantities for clinical use.
2025-08-28 | GSE306748 | GEO
Project description:TERT gene rearrangement with transcriptional super-enhancers leads to substantial TERT over-expression and neuroblastoma. No targeted therapy is available for clinical trials in patients. Here we show that the transcriptional kinases CDK7/CDK9 and the casein kinase CKIα were required for TERT gene over-expression and p53 protein degradation respectively in TERT-rearranged neuroblastoma cells. Co-knockdown of CDK7/CDK9 and CKIα or treatment with the CDK7/CDK9 and CKIα co-inhibitor A51 reduced TERT gene transcriptional initiation, elongation and expression, activated p53 protein expression, co-operatively induced apoptosis and suppressed tumor progression in mouse models. Screening of an approved oncology drug library identified Ceritinib as the agent exerting the best synergistic anticancer effects with A51. A51 and Ceritinib synergistically down-regulated mitochondrial complex I gene expression and induced oxidative stress and TERT-rearranged neuroblastoma cell apoptosis. In mice xenografted with TERT-rearranged patient-derived xenograft neuroblastoma cells, A51 and Ceritinib synergistically induced tumor cell apoptosis, suppressed tumor progression and improved mouse survival. A51 and Ceritinib combination therapy is therefore a good candidate for translation into the first clinical trial of a targeted therapy against TERT-rearranged neuroblastoma.
2026-04-08 | GSE262443 | GEO
Project description:H3K4me3 changes during immortalization of breast cells. The aim of the study was to determine whether differential epigentic state of TERT gene is involved in immortalization of breast cells.
2013-07-03 | GSE48457 | GEO
Project description:H3K27me3 changes during immortalization of breast cells. The aim of the study was to determine whether differential epigentic state of TERT gene is involved in immortalization of breast cells.
2013-07-03 | GSE48456 | GEO
Project description:DNA methylation changes during immortalization of breast cells. The aim of the study was to determine whether differential epigentic state of TERT gene is involved in immortalization of breast cells.
2013-07-03 | GSE48447 | GEO
Project description:Spontaneous immortalization in large animals like cattle is rare and has previously required genetic manipulation of TP53 or TERT. Here, we demonstrate the spontaneous immortalization of fibroblast lines from Holstein and Simmental cows over 500 days of continuous culture, corresponding to 240 population doublings. Initial senescence was observed at population doubling 60, marked by telomere shortening, γH2AX foci, and an active SASP profile. After 400 days, stable immortalized lines with a doubling time of 45 hours emerged. Transcriptomic and metabolic analyses revealed a reversal of senescence-associated apoptotic processes and mitochondrial stress, with no change in telomerase or p53 activity. Our findings suggest bovine fibroblast immortalization can occur through alternative pathways, with applications in cultivated meat production and aging research.
2025-09-08 | GSE282140 | 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