Tao Wang Similar Datasets
Project description:Cellular senescence forms a barrier that inhibits the acquisition of an immortal phenotype, a critical feature in tumorigenesis. The inactivation of multiple pathways that positively regulate senescence are required for immortalization. To identify these pathways in an unbiased manner, we performed DNA microarray analyses to assess the expression of 20,000 genes in human prostate epithelial cells (HPECs) passaged to senescence. These gene expression patterns were then compared with those of HPECs immortalized with the human Papillomavirus 16 E7 oncoprotein. Senescent cells display gene expression patterns that reflect their nonproliferative, differentiated phenotype and express secretory proteases and extracellular matrix components. A comparison of genes transcriptionally up-regulated in senescence to those in which expression is significantly down-regulated in immortalized HPECs identified three genes: the chemokine BRAK, DOC1, and a member of the insulin-like growth factor axis, IGFBP-3. Expression of these genes is found to be uniformly lost in human prostate cancer cell lines and xenografts, and previously, their inactivation was documented in tumor samples. Thus, these genes may function in novel pathways that regulate senescence and are inactivated during immortalization. These changes may be critical not only in allowing cells to bypass senescence in vitro but in the progression of prostate cancer in vivo. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Computed
2005-10-18 | E-GEOD-3460 | biostudies-arrayexpress
Project description:The p53 protein is a cell-autonomous tumor suppressor that restricts malignant transformation by triggering cell cycle exit or apoptosis. p53 also promotes cellular senescence, a program that triggers a stable cell cycle arrest and can modify the tissue microenvironment through its effect on cell membrane and secretory proteins. Here we show that specific ablation of p53 in hepatic stellate cells, which undergo a process of proliferation and senescence in the fibrogenic response to liver damage, enhances liver cirrhosis, reduces survival and increases the malignant transformation of adjacent epithelial cells into hepatocellular carcinoma. This p53-dependent senescence program involves the release of secreted proteins which skew macrophages into a tumor-inhibiting M1-state that can eliminate senescent stellate cells. In contrast, p53-deficient stellate cells secrete factors that promote M2 polarization, which is pro-tumorigenic. Our study reveals that p53 can exert a non-cell-autonomous tumor suppressor response and suggests that this occurs, in part, by its ability to influence macrophage polarization. We used microarrays to detail the global programme of gene expression underlying p53-dependent senescent and identified distinct classes of up-regulated or down-regulated genes during this process. Proliferating and senescent stellate cell pellets were collected RNA extraction and hybridization on Affymetrix microarrays.
2013-04-05 | E-GEOD-39469 | biostudies-arrayexpress
Project description:To identify differentially expressed genes during cellular senescence, we performed transcriptional profiling with RNA sequencing (RNA-seq) before and after senescence induction using a stress-induced senescence model (bleomycin-induced senescence).
2021-03-17 | GSE168994 | GEO
Project description:Cellular senescence forms a barrier that inhibits the acquisition of an immortal phenotype, a critical feature in tumorigenesis. The inactivation of multiple pathways that positively regulate senescence are required for immortalization. To identify these pathways in an unbiased manner, we performed DNA microarray analyses to assess the expression of 20,000 genes in human prostate epithelial cells (HPECs) passaged to senescence. These gene expression patterns were then compared with those of HPECs immortalized with the human Papillomavirus 16 E7 oncoprotein. Senescent cells display gene expression patterns that reflect their nonproliferative, differentiated phenotype and express secretory proteases and extracellular matrix components. A comparison of genes transcriptionally up-regulated in senescence to those in which expression is significantly down-regulated in immortalized HPECs identified three genes: the chemokine BRAK, DOC1, and a member of the insulin-like growth factor axis, IGFBP-3. Expression of these genes is found to be uniformly lost in human prostate cancer cell lines and xenografts, and previously, their inactivation was documented in tumor samples. Thus, these genes may function in novel pathways that regulate senescence and are inactivated during immortalization. These changes may be critical not only in allowing cells to bypass senescence in vitro but in the progression of prostate cancer in vivo.
2013-01-30 | E-SMDB-6 | biostudies-arrayexpress
Project description:The p53 protein is a cell-autonomous tumor suppressor that restricts malignant transformation by triggering cell cycle exit or apoptosis. p53 also promotes cellular senescence, a program that triggers a stable cell cycle arrest and can modify the tissue microenvironment through its effect on cell membrane and secretory proteins. Here we show that specific ablation of p53 in hepatic stellate cells, which undergo a process of proliferation and senescence in the fibrogenic response to liver damage, enhances liver cirrhosis, reduces survival and increases the malignant transformation of adjacent epithelial cells into hepatocellular carcinoma. This p53-dependent senescence program involves the release of secreted proteins which skew macrophages into a tumor-inhibiting M1-state that can eliminate senescent stellate cells. In contrast, p53-deficient stellate cells secrete factors that promote M2 polarization, which is pro-tumorigenic. Our study reveals that p53 can exert a non-cell-autonomous tumor suppressor response and suggests that this occurs, in part, by its ability to influence macrophage polarization. We used microarrays to detail the global programme of gene expression underlying p53-dependent senescent and identified distinct classes of up-regulated or down-regulated genes during this process.
2013-04-05 | GSE39469 | GEO
Project description:Cellular senescence forms a barrier that inhibits the acquisition of an immortal phenotype, a critical feature in tumorigenesis. The inactivation of multiple pathways that positively regulate senescence are required for immortalization. To identify these pathways in an unbiased manner, we performed DNA microarray analyses to assess the expression of 20,000 genes in human prostate epithelial cells (HPECs) passaged to senescence. These gene expression patterns were then compared with those of HPECs immortalized with the human Papillomavirus 16 E7 oncoprotein. Senescent cells display gene expression patterns that reflect their nonproliferative, differentiated phenotype and express secretory proteases and extracellular matrix components. A comparison of genes transcriptionally up-regulated in senescence to those in which expression is significantly down-regulated in immortalized HPECs identified three genes: the chemokine BRAK, DOC1, and a member of the insulin-like growth factor axis, IGFBP-3. Expression of these genes is found to be uniformly lost in human prostate cancer cell lines and xenografts, and previously, their inactivation was documented in tumor samples. Thus, these genes may function in novel pathways that regulate senescence and are inactivated during immortalization. These changes may be critical not only in allowing cells to bypass senescence in vitro but in the progression of prostate cancer in vivo. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set
2005-10-18 | GSE3460 | GEO
Project description:We have generated IMR90-hTERT cells carrying a Doxycyclin-inducible (Tet-On) vector expressing an N-terminally Flag tagged YAP5SA. To identify differentially expressed genes by YAP5SA expression during cellular senescence, we performed transcriptional profiling by RNA sequencing (RNA-seq) with or without YAP5SA expression (using doxycyclin), before and after senescence induction using a stress-induced senescence model (bleomycin-induced senescence).
2025-01-30 | GSE278460 | GEO
Project description:To identify differentially expressed genes by autophagy inhibition during cellular senescence, we performed transcriptional profiling by RNA sequencing (RNA-seq) with or without autophagy inhibition (using a shRNA targeting either ATG7 or ATG13), before and after senescence induction using a stress-induced senescence model (bleomycin-induced senescence)
2024-10-02 | GSE272675 | GEO
Project description:Senescent cells affect many physiological and pathophysiological processes. While select genetic and epigenetic elements for senescence induction have been identified, the dynamics, epigenetic mechanisms and regulatory networks defining senescence competence, induction and maintenance remain poorly understood, precluding the deliberate therapeutic targeting of senescence for health benefits. Here, we examined the possibility that the epigenetic state of enhancers determines senescent cell fate. We explored this by generating time-resolved transcriptomes and epigenome profiles during oncogenic RAS-induced senescence and validating central findings in different cell biology and disease models of senescence. Through integrative analysis and functional validation, we reveal links between enhancer chromatin, transcription factor recruitment and senescence competence. We demonstrate that activator protein 1 (AP-1) 'pioneers' the senescence enhancer landscape and defines the organizational principles of the transcription factor network that drives the transcriptional programme of senescent cells. Together, our findings enabled us to manipulate the senescence phenotype with potential therapeutic implications.
2020-03-18 | GSE143248 | GEO
Project description:Senescent cells affect many physiological and pathophysiological processes. While select genetic and epigenetic elements for senescence induction have been identified, the dynamics, epigenetic mechanisms and regulatory networks defining senescence competence, induction and maintenance remain poorly understood, precluding the deliberate therapeutic targeting of senescence for health benefits. Here, we examined the possibility that the epigenetic state of enhancers determines senescent cell fate. We explored this by generating time-resolved transcriptomes and epigenome profiles during oncogenic RAS-induced senescence and validating central findings in different cell biology and disease models of senescence. Through integrative analysis and functional validation, we reveal links between enhancer chromatin, transcription factor recruitment and senescence competence. We demonstrate that activator protein 1 (AP-1) 'pioneers' the senescence enhancer landscape and defines the organizational principles of the transcription factor network that drives the transcriptional programme of senescent cells. Together, our findings enabled us to manipulate the senescence phenotype with potential therapeutic implications.
2019-06-14 | GSE122918 | GEO