MEF wt versus Med23-/- KO after 20% Serum Stimulation
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE15638 | GEO | 2009/04/14
SECONDARY ACCESSION(S): PRJNA115639
REPOSITORIES: GEO
Similar Datasets
Project description:Affymetrix MOE430A arrays. Mouse embryonic fibroblasts (MEFs) from E11 passaged through crisis. Starved in 0.5% FBS for 16 h then stimulated by 20% serum final concentration for 30 minutes. The purpose was to identify genes affected by the loss of MED23 protein (subunit of the mediator complex). Samples were assayed in duplicate (Set 1 and Set 2) for starved state and serum state cells. Cells starved in low-serum (0.5%) for 16 h then add final conc. 20% FBS for 30 minutes. Harvest total RNA from duplicate samples. One sample set is kept starved and serves as the baseline. The other set is stimulated. This is done for both wild-type cell and the Med23-/- KO cells. We looked for gene expression fold changes greater than 2 (plus or minus) to find genes affected for serum stimulation by the loss of MED23, looking in detail at immediate early genes like Egr1.
2009-04-14 | E-GEOD-15638 | biostudies-arrayexpress
Project description:We examined how MED23 regulates SRF-targeted genes by comparing WT and Med23 KO mouse embryonic fibroblasts (MEFs) in the presence or absence of serum-stimulation (for 30 and 90 min). To investigate whether MAL antagonizes MED23 in the adipocyte lineage program, we compared the gene expression changes resulting from Mal overexpression (oxMal) and Med23 deficiency (siMed23) in 10T1/2 cell.
2012-10-01 | GSE40286 | GEO
Project description:To ensure the rapid response to stimuli, some HSCs are specifically prepared (primed) for tasks involving activation and reconstitution. However, the key factors that regulate the primed state of HSCs are largely unknown. Here we report that Med23 controls the formation of myeloid-primed HSCs. Ablation of Med23 in hematopoietic system leads to lymphocytopenia. Moreover, Med23-deficient HSCs undergo myeloid-biased differentiation and lose the self-renewal capacity. Interestingly, Med23-deficient HSCs are in myeloid-primed state and are much easier to be activated in response to physiological stresses. Mechanistically, Med23 plays essential roles in maintaining stemness genes expression and suppressing myeloid lineage genes expression. Med23 is down-regulated in HSCs and Med23 deletion results in better survival under myeloablative stress. Altogether, our findings identified Med23 as a gatekeeper of the myeloid-primed state of HSCs, thus providing unique insights into the relationship among Med23-mediated transcriptional regulations, the myeloid-primed state of HSCs and HSC activation upon stresses.
2018-07-15 | GSE112358 | GEO
Project description:To ensure the rapid response to stimuli, some HSCs are specifically prepared (primed) for tasks involving activation and reconstitution. However, the key factors that regulate the primed state of HSCs are largely unknown. Here we report that Med23 controls the formation of myeloid-primed HSCs. Ablation of Med23 in hematopoietic system leads to lymphocytopenia. Moreover, Med23-deficient HSCs undergo myeloid-biased differentiation and lose the self-renewal capacity. Interestingly, Med23-deficient HSCs are in myeloid-primed state and are much easier to be activated in response to physiological stresses. Mechanistically, Med23 plays essential roles in maintaining stemness genes expression and suppressing myeloid lineage genes expression. Med23 is down-regulated in HSCs and Med23 deletion results in better survival under myeloablative stress. Altogether, our findings identified Med23 as a gatekeeper of the myeloid-primed state of HSCs, thus providing unique insights into the relationship among Med23-mediated transcriptional regulations, the myeloid-primed state of HSCs and HSC activation upon stresses.
2018-07-15 | GSE112357 | GEO
Project description:We examined how MED23 regulates SRF-targeted genes by comparing WT and Med23 KO mouse embryonic fibroblasts (MEFs) in the presence or absence of serum-stimulation (for 30 and 90 min). To investigate whether MAL antagonizes MED23 in the adipocyte lineage program, we compared the gene expression changes resulting from Mal overexpression (oxMal) and Med23 deficiency (siMed23) in 10T1/2 cell. In MEF cells, we examined SRF-dependent gene expression in three time points (0, 30, 90min) and two conditions (WT and KO). In 10T1/2 cells, we used three treatment conditions (Mal overexpression, Med23 knockdown, and treatment of both Mal overexpression and Med23 knockdown) with control (no treatment).
2012-10-01 | E-GEOD-40286 | biostudies-arrayexpress
Project description:K-RAS activating mutations occur frequently in non-small cell lung cancer (NSCLC), leading to aberrant activation of Ras-MAPK signaling pathway that contributes to the malignant phenotype. However, the development of Ras-targeted therapeutics remains challenging. Here, we show that MED23, a component of the multisubunit Mediator complex that is known to integrate signaling and gene activities, is selectively important for Ras-active lung cancer. By screening a large panel of human lung cancer cell lines with or without a Ras mutation, we found that Med23 RNAi specifically inhibits the proliferation and tumorigenicity of lung cancer cells with hyperactive Ras activity. Med23-deficiency in fibroblasts selectively inhibited the oncogenic transformation induced by Ras but not by c-Myc. Transcription factor ELK1, which is phosphorylated by MAPK for relaying the Ras signaling to MED23, was also required for the Ras-driven oncogenesis. Transcriptiome analysis revealed that MED23 and ELK1 co-regulate a common set of target genes enriched in regulating cell cycle and proliferation to support the Ras-dependency. Furthermore, correlated with the strength of Ras signaling as indicated by the ELK1 phosphorylation level, MED23 was up-regulated by Ras-transformation, and was found to be overexpressed in both Ras-mutated lung cancer cell lines and primary tumor samples. Remarkably, lower Med23 expression predicts better survival in Ras-active lung cancer patients and xenograft mice. Collectively, our findings demonstrate a critical role for MED23 in enabling the 'Ras-addiction' of lung carcinogenesis, thus providing a vulnerable target for the treatment of Ras-active lung cancer. To gain a genome-wide understanding of how MED23 and ELK1 control gene expression in Ras-active lung cancer cells, we performed gene profiling experiments to analyze the transcriptomes from control, si-Med23, or si-Elk1 A549 cells. The si-Ctrl, si-Med23 and si-Elk1 A549 cells were cultured in the normal condition. Then the cells were harvested for RNA extraction and hybridization on Affymetrix microarrays. The analysis contain 9 samples. si-Ctrl cells have three replicates (si-Ctrl#1, si-Ctrl#2 and si-Ctrl#3), and the si-Med23 or si-Elk1 group contains three different cell lines that harbor three different RNAi oligos against Med23 or Elk1 (si-Med23A, B, C and si-Elk1A, B, C).
2013-08-31 | E-GEOD-40517 | biostudies-arrayexpress
Project description:K-RAS activating mutations occur frequently in non-small cell lung cancer (NSCLC), leading to aberrant activation of Ras-MAPK signaling pathway that contributes to the malignant phenotype. However, the development of Ras-targeted therapeutics remains challenging. Here, we show that MED23, a component of the multisubunit Mediator complex that is known to integrate signaling and gene activities, is selectively important for Ras-active lung cancer. By screening a large panel of human lung cancer cell lines with or without a Ras mutation, we found that Med23 RNAi specifically inhibits the proliferation and tumorigenicity of lung cancer cells with hyperactive Ras activity. Med23-deficiency in fibroblasts selectively inhibited the oncogenic transformation induced by Ras but not by c-Myc. Transcription factor ELK1, which is phosphorylated by MAPK for relaying the Ras signaling to MED23, was also required for the Ras-driven oncogenesis. Transcriptiome analysis revealed that MED23 and ELK1 co-regulate a common set of target genes enriched in regulating cell cycle and proliferation to support the Ras-dependency. Furthermore, correlated with the strength of Ras signaling as indicated by the ELK1 phosphorylation level, MED23 was up-regulated by Ras-transformation, and was found to be overexpressed in both Ras-mutated lung cancer cell lines and primary tumor samples. Remarkably, lower Med23 expression predicts better survival in Ras-active lung cancer patients and xenograft mice. Collectively, our findings demonstrate a critical role for MED23 in enabling the “Ras-addiction” of lung carcinogenesis, thus providing a vulnerable target for the treatment of Ras-active lung cancer. To gain a genome-wide understanding of how MED23 and ELK1 control gene expression in Ras-active lung cancer cells, we performed gene profiling experiments to analyze the transcriptomes from control, si-Med23, or si-Elk1 A549 cells.
2013-08-31 | GSE40517 | GEO
Project description:To analysis TCR induced Med23-dependent gene expression programs in T cells, we have employed microarray expression profiling as a discovery platform to identify genes with the potential to be regulated by Med23 in unstimulated or stimulated T cells. Mice CD4 T cells from wildtype and Med23 knockout mice were left unstimulated or stimulated for 6 hr, and gene expression difference was identified among four samples. Expression of seven genes (Med23, IFNg, IL2, Egr2, c-Fos, c-Jun and Foxp1) was validated in the same RNA samples by real-time PCR. TCR induced Med23-dependent gene expression was measured after unstimulation or stimulation for 6 hr in wildtype and Med23 knockout CD4 T cells.
2014-08-27 | E-GEOD-60779 | biostudies-arrayexpress
Project description:we provide evidence that Med23 is involved in the regulation of adult hippocampal neurogenesis in mouse. Med23-deficient NSCs in the SGZ display faster self-renewal activity possibly by reducing cell cycle length, but neuroblasts, immature and mature new-born neurons are reduced.
2020-06-10 | GSE152113 | GEO
Project description:To analysis TCR induced Med23-dependent gene expression programs in T cells, we have employed microarray expression profiling as a discovery platform to identify genes with the potential to be regulated by Med23 in unstimulated or stimulated T cells. Mice CD4 T cells from wildtype and Med23 knockout mice were left unstimulated or stimulated for 6 hr, and gene expression difference was identified among four samples. Expression of seven genes (Med23, IFNg, IL2, Egr2, c-Fos, c-Jun and Foxp1) was validated in the same RNA samples by real-time PCR.
2014-08-27 | GSE60779 | GEO