HepG2 and THP-1 cells, the latter differentiated by phorbol 12-myristate 13-acetate (PMA), were co-cultured and characterized for typical liver-specific functions, such as xenobiotic detoxification, lipid and cholesterol metabolism. Furthermore, liver injury-associated pathways, such as inflammation, were studied. In general, the co-cultivation of these cells produced a pro-inflammatory system, as indicated by increased levels of cytokines (IL-8, TGF-α, IL-6, GM-CSF, G-CSF, TGF-β, and hFGF) in the respective supernatant. Increased expression levels of target genes of the aryl hydrocarbon receptor (AHR), e.g., CYP1A1, CYP1A2 and CYP1B1, were detected, accompanied by the increased enzyme activity of CYP1A1. Moreover, transcriptome analyses indicated a significant upregulation of cholesterol biosynthesis, which could be reduced to baseline levels by lovastatin. In contrast, total de novo lipid synthesis was reduced in co-cultured HepG2 cells. Key events of the adverse outcome pathway (AOP) for fibrosis were activated by the co-cultivation, however, no increase in the concentration of extracellular collagen was detected. This indicates, that AOP should be used with care. In summary, the indirect co-culture of HepG2/THP 1 cells results in an increased release of pro-inflammatory cytokines, an activation of the AHR pathway and an increased enzymatic CYP1A activity.
Indirect co-cultivation of HepG2 with differentiated THP-1 cells induces AHR signalling and release of pro-inflammatory cytokines.
Treatment
View SamplesMicroRNA microarrays and RNA expression arrays were used to identify functional signaling between neural stem cell progenitor cells (NSPC) and brain endothelial cells (EC) that are critical during embryonic development and tissue repair following brain injury.
The role of microRNAs in neural stem cell-supported endothelial morphogenesis.
Specimen part, Disease, Treatment
View SamplesWe sequenced mRNA from HCT116 p21-/- cells treated with Nutlin-3a, doxorubicin, or DMSO for 24 h. Overall design: Examination of mRNA levels from HCT116 p21-/- cells treated with Nutlin-3a, doxorubicin, or DMSO for 24 h using four replicates each.
Integration of TP53, DREAM, MMB-FOXM1 and RB-E2F target gene analyses identifies cell cycle gene regulatory networks.
No sample metadata fields
View SamplesDuring an incompatible or compatible interaction between rice (Oryza sativa) and the Asian rice gall midge (Orseolia oryzae), a lot of genetic reprogamming occurs in the plant host
Metabolic and transcriptomic changes induced in host during hypersensitive response mediated resistance in rice against the Asian rice gall midge.
No sample metadata fields
View SamplesThe transcription factor MyoD can coax na?e fibroblasts or otherwise committed cells to adopt the skeletal muscle phenotype by activating the muscle gene expression program. Activation of muscle gene expression occurs in quantal steps with not all the target genes of MyoD being activated at the same time. Some genes are induced in the initial phases, others at later stages despite the fact that MyoD is present throughout the differentiation process. MyoD is post-translationally modified by phosphorylation, ubiquitination, and acetylation. Here, we have employed a model system in which MyoD and its non-acetylatable version were inducibly expressed in mouse embryonic fibroblasts derived from mice to investigate how MyoD acetylation may contribute to differential gene activation.
MyoD acetylation influences temporal patterns of skeletal muscle gene expression.
No sample metadata fields
View SamplesLow-oxygen tolerance is supported by an adaptive response that includes a coordinate shift in metabolism and the activation of a transcriptional program that is driven by the hypoxia-inducible factor (HIF) pathway. The precise contribution of HIF-1 in the adaptive response, however, has not been determined. Here we investigate how HIF-1 influences hypoxic adaptation throughout Drosophila development. We find that hypoxic-induced transcriptional changes are comprised of HIF-dependent and HIF-independent pathways that are distinct and separable. We show that normoxic set-points of carbohydrate metabolites are significantly altered in dHIF mutants and that these animals are unable to mobilize glycogen in hypoxia. Furthermore, we find that the estrogen-related receptor (dERR), which is a global regulator of aerobic glycolysis in larvae, is required for a competent hypoxic response. dERR binds to dHIF and participates in the HIF-dependent transcriptional program in hypoxia. In addition, dERR acts in the absence of dHIF in hypoxia and a significant portion of HIF-independent transcriptional responses can be attributed to dERR actions, including upregulation of glycolytic transcripts. These results indicate that competent hypoxic responses arise from complex interactions between HIF-dependent and -independent mechanisms, and that dERR plays a central role in both of these programs.
HIF- and non-HIF-regulated hypoxic responses require the estrogen-related receptor in Drosophila melanogaster.
Specimen part
View SamplesThe objective of this study was to determine the effect of Thyroid Hormone Responsive Protein Spot14 (Spot14) overexpression on the gene expression profiles of tumors from MMTV-Neu mice. Hemizygous MMTV-Neu and MMTV-Spot14 mice were bred and 1 cm tumors from Neu control or Neu/Spot14 bitransgenic offspring were profiled using Affymetrix gene arrays. Tumors from Neu/Spot14 mice emerged significantly earlier than controls, but expressed many genes associated with lactogenic differentiation and were not highly metastatic. These results from the mouse model are consistent with observations from primary human breast tumors, which indicate that high Spot14 gene expression was directly correlated with a luminal subtype and a positive ER status. Overexpression of Spot14 in cultured mammary epithelial cells stimulated proliferation but not differentiation. Together, these data suggest that, in vivo, Spot14 is expressed in well-differentiated cells, and promotes the expansion of this population in the context of oncogenic signaling pathway activation.
Modulation of tumor fatty acids, through overexpression or loss of thyroid hormone responsive protein spot 14 is associated with altered growth and metastasis.
Specimen part
View SamplesWe performed a transcriptomic analysis to identify genes differentially transcribed in the maize stem upon corn borer feeding and treatment with insects regurgitates by using the MACE (Massive Analysis of cDNA Ends) technology. Overall design: Two comparisons were performed: Insect chewing vs control and Regurgitate+wounding vs wounding in three biological replicates per treatment
Maize Stem Response to Long-Term Attack by <i>Sesamia nonagrioides</i>.
Specimen part, Treatment, Subject
View SamplesThe objective of this study was to determine the effect of Thyroid Hormone Responsive Protein Spot14 (Spot14) loss on the gene expression profiles of tumors from MMTV-Polyomavirus middle-T antigen (PyMT) mice. MMTV-PyMT/S14-heterozygous mice were crossed with S14-heterozygous mice and 1 cm tumors from MMTV-PyMT control (wild-type S14) or MMTV-PyMT/S14-null offspring were profiled using Affymetrix gene arrays. Tumor latency was not different between groups; however, tumors lacking S14 grew significantly slower than control tumors. Loss of S14 also decreased the levels of de novo synthesized fatty acids in mammary tumors. In additional studies, performed on MMTV-Neu mice, we found that S14 overexpression was associated with increased tumor cell proliferation and elevated levels of tumor fatty acids. Gene expression profiling revealed that S14 loss and overexpression in mouse mammary tumors altered pathways associated with proliferation and metabolism. This study provides important information about the role of S14 in mammary tumorigenesis and tumor metabolism.
Modulation of tumor fatty acids, through overexpression or loss of thyroid hormone responsive protein spot 14 is associated with altered growth and metastasis.
No sample metadata fields
View SamplesUpon pathogenic infection, drosophila larval host mounts an immune response. Parasitic wasps inject venom that contain virulence factors during oviposition, which can elicit host immune response, and in some cases, suppress host immune responses altogether. Several microarray experiments have been performed on different classes of parasitic wasps. We wanted to compare how Ganaspis xanthopoda-infected hosts respond compared to other classes of parasitic wasps.
A database for the analysis of immunity genes in Drosophila: PADMA database.
Time
View Samples