Conserved transcriptomic signatures and protein markers in cellular senescence models
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ABSTRACT:
PROVIDER: PRJNA987602 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25032574.fastq.gz | Fastqsanger.gz | |||
| SRR25032575.fastq.gz | Fastqsanger.gz | |||
| SRR25032576.fastq.gz | Fastqsanger.gz | |||
| SRR25032577.fastq.gz | Fastqsanger.gz | |||
| SRR25032578.fastq.gz | Fastqsanger.gz |
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Project description:Cellular senescence is described as an irreversible cell cycle arrest induced in response to various stresses. Senescent cells are characterised by heterogeneous signalling alterations, complex secretory phenotype, known as senescence-associated secretory phenotype (SASP), and diverse transcriptomic profile. With the aim to investigate senescence heterogeneity and identify conserved transctiptomic alterations and universal senescence markers, we performed RNA-seq and multiplex proteomic analysis in proteasome inhibition-induced and stress-induced premature senescence models of HFL1 and BJ human fibroblasts. Our data revealed diverse transcriptomic signatures, but also, 231 common differentially expressed genes related to cell division and ECM remodelling, and enriched pathways that remained conserved among the different models with senescence onset. Moreover, we identified a subset of proteins and validated them in replicative senescent models. These proteins are involved in cell cycle arrest and promote a pro-inflammatory environment in premature and replicative senescence models. We suggest that the simultaneous analysis of p21, p-c-JUN, BCL-xL and survivin in cellular lysates, and IL-8, GM-CSF, GDF-15 and GROa in culture supernatants can provide a powerful tool for the identification and monitoring of senescent cells and can support the assessment of the efficacy of potential senotherapeutic approaches.
2023-07-17 | GSE235768 | GEO
Project description:We established parallel replicative and doxorubicin-induced senescence models in human BJ fibroblasts, demonstrating progressive morphological changes and SA-β-gal activity increases across passages (P3-P33). Molecular analyses confirmed expected senescence markers: p21/p53 upregulation and LMNB1 downregulation at RNA/protein levels. Transcriptomic profiling identified 734 upregulated (extracellular matrix organization) and 195 downregulated (cell cycle) genes. Comparative lncRNA analysis revealed 23 consistently upregulated candidates, with PURPL showing the most dramatic senescence-associated induction. These validated models provide a robust platform for mechanistic aging studies, with PURPL emerging as a key regulator of cellular senescence.
2025-12-02 | GSE301164 | GEO
Project description:Abstract: Cellular senescence, an integral component of aging and cancer, arises in response to diverse triggers, including telomere attrition, macromolecular damage, and signaling from activated oncogenes. At present, senescent cells are identified by the combined presence of multiple traits, such as senescence-associated protein expression and secretion, DNA damage, and β-galactosidase activity; unfortunately, these traits are neither exclusively nor universally present in senescent cells. To identify robust shared markers of senescence, we have performed RNA-sequencing analysis across 8 diverse models of senescence triggered in human diploid fibroblasts (WI-38, IMR-90) and endothelial cells (HUVEC, HAEC) by replicative exhaustion, exposure to ionizing radiation or doxorubicin, and expression of the oncogene HRASG12V. The intersection of the altered transcriptomes revealed 47 RNAs consistently elevated and 26 RNAs consistently reduced across all senescence models, including many protein-coding mRNAs and some long noncoding RNAs. We propose that these shared transcriptome profiles will enable the identification of senescent cells in vivo, the investigation of their roles in aging and malignancy, and the development of strategies to target senescent cells therapeutically.
2019-06-12 | GSE130727 | GEO
Project description:Sprague-Dawley (SD) rat pups exposed to room air (NOX) or 95% O2 (HOX) from P1-P10 to study the role of cellular senescence in bronchopulmonary dysplasia (BPD). Markers of cellular senescence in the lungs were obtained at P10 and P21. ScRNAseq of the lungs were obtained at P10 to study cell type-specific cellular senescence.
2024-09-01 | GSE242310 | GEO
Project description:Here, through single-cell transcriptional profiling of genetically homogenous clonal cell lines, we analyzed subpopulations in all three major forms of senescence, namely Oncogene Induced Senescence (OIS), Replicative Senescence (RS), and DNA Damage Induced Senescence (DDIS).
2023-05-04 | GSE173879 | GEO
Project description:Background More than 70% of cancer patients who underwent cranial radiotherapy have cognitive problems, suggesting that they might undergo accelerated brain aging due to the cancer treatment. Radiotherapy is known to induce cellular senescence in tumors and in various cell types in vitro. Therefore, we hypothesized that cranial radiotherapy induces cellular senescence in the brain. Methods We treated male C57BL/6 mice with various dosages of (fractionated) CT-guided cranial radiotherapy. The brains were analyzed for various senescence and glial markers using immunohistochemistry, histochemistry, Cosmx SMI and RT-qPCR. To contextualize the findings regarding cranial radiotherapy in young animals and assess whether these changes parallel natural aging, we studied the brains from 77-week-old female mice, which is considered middle-aged to old representing early aging. Results Surprisingly, we found no increase in markers for cellular senescence in the brain after cranial radiotherapy. However, we did detect profound changes in different types of glia. In early-aged mice we again did not detect an increase in senescence markers, but we observed the same directionality in the effects on glia. These effects on glia were milder compared to those upon cranial radiotherapy. Conclusion Overall, cellular senescence in the healthy brain seems a rather uncommon phenomenon and not induced upon cranial radiotherapy, but profound changes in different types of glia were detected upon cranial radiotherapy.
2025-06-17 | GSE283863 | GEO
Project description:Senescence associated gene signatures
| PRJNA811141 | ENA
Project description:Blocking of nucleocytoplasmic trafficking is an essential feature of replicative senescence (RS). However, whether nuclear barrier per se causes cellular senescence still remains elusive. Here, we show that nuclear barrier induced by blocking nucleocytoplasmic trafficking, especially nuclear export, elicits RS-like changes in SA-β-gal activity, DNA damage, and expression of cell cycle regulators. Comparative transcriptome analysis revealed that nuclear barrier-induced senescence (NBIS) was most similar in gene expression changes to RS compared to senescence induced by stresses (oxidative stress, DNA damage and oncogene), implying that nuclear barrier induces RS-like physiological senescence-associated changes. Shared senescence-related processes between NBIS and RS included lysosomal degradation, nuclear transport, and translation, resulting in coordinated reduction in transmission of extrinsic signals to nucleus and intracellular protein supply from nucleus. Notably, these processes were conserved in yeast aging. Therefore, we propose NBIS as a novel modality of cellular senescence, representing the fundamental nature of physiological aging in eukaryotes.
2021-06-17 | GSE112530 | GEO
Project description:Cellular senescence is a program of irreversible cell cycle arrest that normal cells undergo in response to progressive shortening of telomeres, changes in telomeric structure, oncogene activation or oxidative stress. The underlying signalling pathways, potentially of major clinicopathological relevance, are unknown. A major stumbling block to studying senescence has been the absence of suitable model systems because of the asynchrony of this process in heterogeneous cell populations. To simplify this process many investigators study oncogene-induced senescence due to expression of activated oncogenes where senescence occurs prematurely without telomere attrition and can be induced acutely in a variety of cell types. We have taken a different approach by making use of the finding that reconstitution of telomerase activity by introduction of the catalytic subunit of human telomerase alone is incapable of immortalising all human somatic cells, but inactivation of the p16-pRB and p53-p21 pathways are required in addition. The ability of SV40 large T antigen to inactivate the p16-pRB and p53-p21 pathways has enabled us to use a thermolabile mutant of LT antigen, in conjunction with hTERT, to develop conditionally immortalised human (HMF3A) fibroblasts that are immortal but undergo an irreversible growth arrest when the thermolabile LT antigen is inactivated leading to activation of pRB and p53. When these cells cease dividing, senescence-associated- b-galactosidase activity is induced and the growth-arrested cells have morphological features and express genes in common with senescent cells. Since these cells growth arrest in a synchronous manner they are an excellent starting point for dissecting the pathways that underlie cellular senescence and act downstream of p16-pRB and p53-p21 pathways. We have combined genome-wide expression profiling with genetic complementation to undertake identification of genes that are differentially expressed when these conditionally immortalised human fibroblasts undergo senescence upon activation of the p16-pRB and p53-p21 tumour suppressor pathways. Genes differentially expressed upon senescence will be identified by comparing arrays from growing versus senescent cells. Changes in gene expression due to the temperature shift will be eliminated by comparing with array data from the non-conditional HMF3S cells grown at 34°C ±0.5°C and 38°C ±0.5°C. To determine if the changes in gene expression upon senescence are specific and reversible, the set of differential genes will then be overlaid with array data from cells in which senescence has been bypassed by inactivation of the p16-pRB and p53-p21 tumour suppressor pathways
2011-01-21 | E-GEOD-24810 | biostudies-arrayexpress
Project description:Senescent cells exhibit a reduced response to intrinsic and extrinsic stimuli. This reduction could be explained by disrupted nuclear transmission of signals. However, this hypothesis required more evidence to complete as a new modality of cellular senescence. Proteomic analysis of the cytoplasmic and nuclear fractions from young and senescent cells revealed disruption of nucleocytoplasmic trafficking (NCT) as an essential feature of replicative senescence (RS) at the global level. Blocking NCT either chemically or genetically induced RS-like senescence phenotypes, named as nuclear barrier-induced senescence (NBIS). Transcriptomic analysis revealed that NBIS had the most similar gene expression pattern to RS, compared with other stress-induced types of cellular senescence. Core proteomic and transcriptomic shared patterns between RS and NBIS included upregulation of endocytosis-lysosome network and downregulation of NCT in senescent cells, which were also conserved in yeast aging model. These results implicate an aging-dependent coordinated reduction in the transmission of extrinsic signals to the nucleus and in the nucleus-to-cytoplasm supply of proteins/RNAs. We further showed that the aging-associated decrease in Sp1 transcription factor expression was responsible for downregulation of NCT. Our results suggest that NBIS is a modality of cellular senescence that can represent the nature of physiological aging in eukaryotes.
2021-06-18 | PXD025618 | Pride