Alteration of gene expression by AIMP3 depletion in mouse embryonic stem cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE104241 | GEO | 2017/09/27
SECONDARY ACCESSION(S): PRJNA412154
REPOSITORIES: GEO
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Project description:Both p53 and the Wnt signaling pathways play important roles in tumorigenesis and development. However, few studies, particularly on a genome-wide scale, have linked these two pathways. Here we show that p53 directly regulates the Wnt signaling pathway in murine embryonic stem cells (mESCs) using an integrated genome-wide approach. A chromatin-immunoprecipitation-based microarray assay (ChIP-chip) reveals that the Wnt signaling pathway is significantly over-represented in p53 bound genes. Using gene expression microarray and real-time PCR, we demonstrate that the expressions of many Wnts are robustly induced by various stresses, including DNA damage and hypoxia that activate p53. Importantly, the activation of p53 is a prerequisite for the induction of Wnts. Moreover, conditional medium (CM) collected from ultraviolet (UV)-treated mESCs contains an anti-differentiation activity, which can be lowered by either the addition of Wnt signaling inhibitors into the CM or the reduction of p53 levels in UV-treated mESCs. These results suggest that stressed mESCs utilize the p53-Wnt signaling axis to signal neighboring mESCs to delay the differentiation. Together, our results uncover a novel connection between p53 and the Wnt signaling pathways in mediating cell-to-cell communication in mESCs, and provide insights into the functions of these two pathways in tumorigenesis and development
2010-01-19 | GSE16427 | GEO
Project description:Genome-wide analysis of gene expression changes in murine embryonic stem cells (R1E cells) treated with Ultraviolet and adriamycin Both p53 and the Wnt signaling pathways play important roles in tumorigenesis and development. However, few studies, particularly on a genome-wide scale, have linked these two pathways. Here we show that p53 directly regulates the Wnt signaling pathway in murine embryonic stem cells (mESCs) using an integrated genome-wide approach. A chromatin-immunoprecipitation-based microarray assay (ChIP-chip) reveals that the Wnt signaling pathway is significantly over-represented in p53 bound genes. Using gene expression microarray and real-time PCR, we demonstrate that the expressions of many Wnts are robustly induced by various stresses, including DNA damage and hypoxia that activate p53. Importantly, the activation of p53 is a prerequisite for the induction of Wnts. Moreover, conditional medium (CM) collected from ultraviolet (UV)-treated mESCs contains an anti-differentiation activity, which can be lowered by either the addition of Wnt signaling inhibitors into the CM or the reduction of p53 levels in UV-treated mESCs. These results suggest that stressed mESCs utilize the p53-Wnt signaling axis to signal neighboring mESCs to delay the differentiation. Together, our results uncover a novel connection between p53 and the Wnt signaling pathways in mediating cell-to-cell communication in mESCs, and provide insights into the functions of these two pathways in tumorigenesis and development.
2010-01-19 | GSE16428 | GEO
Project description:To explore the mechanism by which PRMT7 regulates HCC cell malignant phenotypes, we performed RNA-seq in QGY-7703 cells before and after PRMT7 knockdown to identify the affected signaling pathways. 296 differentially expressed genes were identified in PRMT7-downregulated cells (Figure 6A) and these genes were enriched in cancer-related pathways including MAPK signaling pathway, p53 signaling pathway, and FoxO signaling pathway (Figure 6B), as revealed by DAVID KEGG analysis.
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Project description:JMJD2B is expressed in a high proportion of human breast tumors, and the expression levels significantly correlate with estrogen receptor (ER) positivity. To assess the effect of JMJD2B depletion on the ER signaling pathway, we performed genome-wide gene expression analysis using the Affymetrix Human Gene 1.0 ST array. RNA was extracted from steroid-depleted control MCF-7 cells (control E2(-)), control MCF-7 cells treated with E2 (control E2(+)), steroid-depleted JMJD2B-depleted MCF-7 cells (siJ2B E2(-)), and JMJD2B-depleted MCF-7 cells treated with E2 (siJ2B E2(+)).
2010-12-31 | E-GEOD-23445 | biostudies-arrayexpress
Project description:Mouse ESCs depleted of the epigenetic modifying enzyme Usp22 fail to differentiate properly. Ectopic expresison of Usp22 results in spontaneous differnetiation. In order to understand the transcriptional program underlying this biological defect, whole genome expression analysis was performed. E14 mESCs were infected with lentivirus containing shRNA targeting Usp22 or control (Luc). RNA was extracted from both samples and subjected to expression analysis by affymetrix array.
2013-05-15 | E-GEOD-42934 | biostudies-arrayexpress
Project description:Authors: David R. Amici, Sammy Alhayek, Austin T. Klein, Yi-Zhi Wang, Anika P. Wilen, Weimin Song, Pei Zhu, Abhishek Thakkar, McKenzi A. King, Adam Steffeck, Milad J. Alasady, Clara Peek, Jeffrey N. Savas, Marc L. Mendillo*
ABSTRACT
The recently discovered HAPSTR1 protein broadly oversees cellular stress responses. This function requires HUWE1, a ubiquitin ligase which paradoxically marks HAPSTR1 for degradation, but much about this pathway remains unclear. Here, leveraging multiplexed proteomics, we find that HAPSTR1 enables nuclear localization of HUWE1 with implications for nuclear protein quality control. We show that HAPSTR1 is tightly regulated and identify ubiquitin ligase TRIP12 and deubiquitinase USP7 as upstream regulators titrating HAPSTR1 stability. Finally, we generate conditional Hapstr1 knockout mice, finding that Hapstr1-null mice are perinatal lethal, adult mice depleted of Hapstr1 have reduced fitness, and primary cells explanted from Hapstr1-null animals falter in culture coincident with HUWE1 mislocalization and broadly remodeled signaling. Notably, while HAPSTR1 potently suppresses p53, we find that Hapstr1 is essential for life even in mice lacking p53. Altogether, we identify novel components and functional insights into the conserved HAPSTR1-HUWE1 pathway and demonstrate its requirement for mammalian life.
2024-02-26 | MSV000094168 | MassIVE
Project description:Transcriptome analysis of human OXR1 depleted cells reveals its role in regulating the p53 signaling pathway
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Project description:Mitochondrial DNA-depleted human skin fibroblasts (HSF rho0) with suppressed oxidative phosphorylation were characterized by significant changes in the expression of 2100 nuclear genes, encoding numerous protein classes, in NF-kappaB and STAT3 signaling pathways and by decreased activity of the mitochondrial death pathway, compared to the parent rho+ HSF. In contrast, the extrinsic TRAIL/TRAIL-Receptor-mediated death pathway remained highly active, and exogenous TRAIL induced higher levels of apoptosis in rho0 cells compared to rho+ HSF. Global gene expression analysis using microarray and quantitative RT-PCR demonstrated that expression levels of many growth factors and their adaptor proteins (FGF13, HGF, IGFBP4, IGFBP6, IGFL2), cytokines (IL6, IL17B, IL18, IL19, IL28B) and cytokine receptors (IL1R1, IL21R, IL31RA) were substantially decreased after mitochondrial depletion. Some of these genes were targets of NF-kappaB and STAT3, and their protein products could regulate the STAT3 signaling pathway. Alpha-irradiation induced expression of several NF-kappaB/STAT3 target genes, including IL1A, IL1B, IL6, PTGS2/COX2 and MMP12, in rho+ HSF, but this response was substantially decreased in rho0 HSF. Suppression of the IKK-NF-kappaB pathway by the small molecular inhibitor BMS-345541 and of the JAK2-STAT3 pathway by AG490 dramatically increased TRAIL-induced apoptosis in the control and irradiated rho+ HSF. Inhibitory antibodies against IL6, the main activator of JAK2-STAT3 pathway, added into the cell media, also increased TRAIL-induced apoptosis in rho+ HSF. However, NF-kappaB activation was partially lost in mitochondrial DNA-depleted HSF resulting in downregulation of the basal or radiation-induced expression of numerous NF-kappaB targets, further suppressing IL6-JAK2-STAT3, that in concert with NF-kappaB, regulated protection against TRAIL-induced apoptosis. There are 12 total samples, 3 biological replicates each of HSF rho+ and rho0 cells that were not irradiated (control=C) or irradiated (alpha=A). Cells were harvested at 4 hours after treatment.
2011-04-04 | E-GEOD-24945 | biostudies-arrayexpress
Project description:The TET family of FE(II) and 2-oxoglutarate-dependent enzymes (Tet1/2/3) promote DNA demethylation by converting 5-methylcytosine to 5-hydroxymethylcytosine (5hmC), which they further oxidize into 5-formylcytosine and 5-carboxylcytosine. Tet1 is robustly expressed in mouse embryonic stem cells (mESCs) and has been implicated in mESC maintenance. Here we demonstrate that, unlike genetic deletion, RNAi-mediated depletion of Tet1 in mESCs led to a significant reduction in 5hmC and loss of mESC identity. The differentiation phenotype due to Tet1 depletion positively correlated with the extent of 5hmC loss. Meta-analyses of genomic datasets suggested interaction between Tet1 and leukemia inhibitory factor (LIF) signaling. LIF signaling is known to promote self-renewal and pluripo-tency in mESCs partly by opposing MAPK/ERK mediated differentiation. Withdrawal of LIF leads to differentiation of mESCs. We discovered that Tet1 depletion impaired LIF-dependent Stat3-mediated gene activation by affecting Stat3's ability to bind to its target sites on chromatin. Nanog overexpression or inhibition of MAPK/ERK signaling, both known to maintain mESCs in the absence of LIF, rescued Tet1 depletion, further supporting the dependence of LIF/Stat3 signaling on Tet1. These data support the conclusion that analysis of mESCs in the hours/days immediately following efficient Tet1 depletion reveals Tet1M-bM-^@M-^Ys normal physiological role in maintaining the pluripotent state that may be subject to homeostatic compensation in genetic models. Genome-wide mapping of 5hmC and microarray gene expression profiling in E14Tg2a mESCs after transfection with indicated siRNAs: Tet1 siRNA #1 (Invitrogen, MSS284895), Tet1 siRNA #2 (Invitrogen, MSS284897), and Control siRNA duplex targeting firefly luciferase.
2012-01-06 | E-GEOD-34886 | biostudies-arrayexpress
Project description:The TET family of FE(II) and 2-oxoglutarate-dependent enzymes (Tet1/2/3) promote DNA demethylation by converting 5-methylcytosine to 5-hydroxymethylcytosine (5hmC), which they further oxidize into 5-formylcytosine and 5-carboxylcytosine. Tet1 is robustly expressed in mouse embryonic stem cells (mESCs) and has been implicated in mESC maintenance. Here we demonstrate that, unlike genetic deletion, RNAi-mediated depletion of Tet1 in mESCs led to a significant reduction in 5hmC and loss of mESC identity. The differentiation phenotype due to Tet1 depletion positively correlated with the extent of 5hmC loss. Meta-analyses of genomic datasets suggested interaction between Tet1 and leukemia inhibitory factor (LIF) signaling. LIF signaling is known to promote self-renewal and pluripo-tency in mESCs partly by opposing MAPK/ERK mediated differentiation. Withdrawal of LIF leads to differentiation of mESCs. We discovered that Tet1 depletion impaired LIF-dependent Stat3-mediated gene activation by affecting Stat3's ability to bind to its target sites on chromatin. Nanog overexpression or inhibition of MAPK/ERK signaling, both known to maintain mESCs in the absence of LIF, rescued Tet1 depletion, further supporting the dependence of LIF/Stat3 signaling on Tet1. These data support the conclusion that analysis of mESCs in the hours/days immediately following efficient Tet1 depletion reveals Tet1’s normal physiological role in maintaining the pluripotent state that may be subject to homeostatic compensation in genetic models. Genome-wide mapping of 5hmC and microarray gene expression profiling in E14Tg2a mESCs after transfection with indicated siRNAs: Tet1 siRNA #1 (Invitrogen, MSS284895), Tet1 siRNA #2 (Invitrogen, MSS284897), and Control siRNA duplex targeting firefly luciferase.
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