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GSE33100
Drosophila melanogaster
26 Downloadable Samples
Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Low-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.
Publication Title
HIF- and non-HIF-regulated hypoxic responses require the estrogen-related receptor in Drosophila melanogaster.
Sample Metadata Fields
Specimen part
View Samples- Ovis aries
- 29 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Body size varies enormously among mammalian species. In small mammals, body growth is typically suppressed rapidly, within weeks, whereas in large mammals, growth is suppressed slowly, over years, allowing for a greater adult size. We recently reported evidence that body growth suppression in rodents is caused in part by a juvenile genetic program that occurs in multiple tissues simultaneously and involves the downregulation of a large set of growth-promoting genes. We hypothesized that this genetic program is conserved in large mammals but that its time course is evolutionarily modulated such that it plays out more slowly, allowing for more prolonged growth. Consistent with this hypothesis, using expression microarray analysis, we identified a set of genes that are downregulated with age in both juvenile sheep kidney and lung. This overlapping gene set was enriched for genes involved in cell proliferation and growth and showed striking similarity to a set of genes downregulated with age in multiple organs of the juvenile mouse and rat, indicating that the multiorgan juvenile genetic program previously described in rodents has been conserved in the 80 million years since sheep and rodents diverged in evolution. Using microarray and real-time PCR, we found that the pace of this program was most rapid in mice, more gradual in rats, and most gradual in sheep. The findings support the hypothesis that a growth-regulating genetic program is conserved among mammalian species but that its pace is modulated to allow more prolonged growth and therefore greater adult body size in larger mammals.
Publication Title
Evolutionary conservation and modulation of a juvenile growth-regulating genetic program.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 2500
Description
Transcriptomic analysis of H3.3 KO/Kd mouse embryonic fibroblasts (MEFs) Overall design: We isolated total RNA from control shRNA treated or shH3.3A treated H3.3B KO MEFs and carried out Ribozero RNA-seq analysis. RNA-seq analysis was carried out on pooled datasets from biological duplicate experiments.
Publication Title
Histone H3.3 regulates mitotic progression in mouse embryonic fibroblasts.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 39 Downloadable Samples
- IlluminaHiSeq1000, IlluminaHiSeq1500
Description
The goal of this study is to simultaneously interrogate the gene expression programs in human host cells (human foreskin fibroblasts) infected with the intracellular parasite Trypanosoma cruzi. We conducted high-resolution sequencing of the transcriptomes of T. cruzi and infected human foreskin fibroblasts (HFFs) using an RNA-seq approach. An array of computational tools was applied to map reads to the T. cruzi and human genomes and reconstruct full-length transcripts. mRNA abundance was determined for T. cruzi genes at at various time points post-infection enabling us to identify co-expression patterns that correlate with the biology of the parasite. We also conducted a time course of infection in host cells to obtain a preliminary analysis of the dynamic nature of parasite and host cell gene expression programs in the context of infection. These data provide the first glimpse of T. cruzi gene expression programs that are uniquely activated in the context of intracellular infection along with the transcriptional response of the human host cell. The study provides a solid framework for future functional and genomic studies of Chagas disease as well as intracellular pathogenesis in general.
Publication Title
Transcriptome Remodeling in Trypanosoma cruzi and Human Cells during Intracellular Infection.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Hopx is a transcription co-factor expressed during lung development and we wanted to profile Hopx +/+ and -/- embyonic lungs. Results inform the role of Hopx in embryonic lung development
Publication Title
Plasticity of Hopx(+) type I alveolar cells to regenerate type II cells in the lung.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 120 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Colorectal carcinoma is the third leading cause of cancer-related death in the United States. In order to understand the mechanism/signaling pathways responsible for invasion, migration and metastasis in colorectal cancer, we developed an integrative and comparative genetic approach to infer transcriptional regulatory mechanisms underlying colon cancer progression. Accordingly, we filtered fourteen human colorectal cancer (CRC) microarray data sets, from an immune competent mouse model of metastasis to identify known and novel transcriptional regulators in CRC. Using this approach, Nuclear Factor of Activated T cells (NFAT) family of transcription factors were identified as metastasis driver of colon cancer. NFAT family of transcription factors is known to induce gene transcription in various disease processes, including carcinogenesis. We used parental and metastatic derivatives of MC38 mouse colon cancer cells (MC38Par and MC38Met, respectively) to evaluate the role of NFATc1 in cancer cell invasiveness. We found that high NFATc1 expression correlates with significantly increased (p<0.0001) Trans-Endothelial Invasion (TEI) in MC38Met cells. Conversely, RNAi-based inhibition of NFATc1 expression and functional inhibition with calcineurin inhibitor FK506 in MC38Met cells, both resulted in significant decreased TEI (p=0.0193 & p=0.0003). Furthermore, a set of predicted NFATc1 target mRNAs identified in our original analysis were downregulated by knock-down of NFATc1 or functional inhibition with FK506 in MC38Met cells. The expression level (mRNA) of predicted gene targets were high in human CRC specimens which had higher than median NFATc1 mRNA expression (n=11 out of total 22). The tumor-associated NFATc1 co-regulated gene signature is significantly correlated with both disease-specific and disease-free survival in Stage II and III CRC patients. We have successfully demonstrated a bioinformatics approach to identify a tumor promoter driver gene NFATc1. Our studies suggest a role of NFATc1 towards invasion and its co-regulated gene signature for poor outcomes in colorectal cancer.
Publication Title
Nuclear factor of activated T-cell activity is associated with metastatic capacity in colon cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- NextSeq 500
Description
E-cadherin (E-cad) mediates cell-cell adhesion and has been proposed to suppress both invasion and metastasis. However, invasive ductal cancers retain E-cad expression in the primary tumor, circulating tumor cells, and distant metastases. We recently demonstrated that cancer cell clusters are efficient metastatic seeds. Since clusters organize through cell-cell adhesion, we tested the requirement for E-cad in genetically engineered mouse models of luminal and basal breast cancer. Loss of E-cad increased invasion and dissemination in 3D culture and in the mammary gland. However, E-cad loss also reduced cancer cell proliferation, survival, tumor cell seeding, and metastatic outgrowth in the lungs. At the transcript level, loss of E-cad was associated with increased apoptosis. Consistent with these results, inhibition of apoptosis partially rescued the metastatic phenotype of E-cad null cancer cells. We therefore propose that E-cad is an invasion suppressor, survival factor, and metastasis promoter in invasive ductal cancers. Overall design: Differential gene expression analysis between organoids isolated from adeno-Cre transduced MMTV-PyMT E-cad+/+ (r = 4 biological replicates) and adeno-Cre transduced MMTV-PyMT E-cadfl/fl (r = 5 biological replicates)
Publication Title
E-cadherin is required for metastasis in multiple models of breast cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 507 Downloadable Samples
- Illumina HiSeq 2500
Description
Despite widespread interest in using human stem cells in neurological disease modeling, a suitable model system to study human neuronal connectivity is lacking. Here, we report a protocol for efficient differentiation of hippocampal pyramidal neurons and an in vitro model for hippocampal neuronal connectivity. We developed an embryonic stem cell (ESC)- and induced pluripotent stem cell (iPSC)-based protocol to differentiate human CA3 pyramidal neurons from patterned hippocampal neural progenitor cells (NPCs). This differentiation induces a comprehensive patterning and generates multiple CA3 neuronal subtypes. The differentiated CA3 neurons are functionally active and readily form neuronal connection with dentate granule (DG) neurons in vitro, recapitulating the synaptic connectivity within the hippocampus. When we applied this neuronal co-culture approach to study connectivity in schizophrenia, we found deficits in spontaneous activity in patient iPSC derived DG–CA3 co-culture by multi-electrode array recording. In addition, both multi-electrode array recording and whole cell patch clamp electrophysiology revealed a reduction in spontaneous and evoked neuronal activity in CA3 neurons derived from schizophrenia patients. Altogether these results underscore the relevance of this new model in studying diseases with hippocampal vulnerability. Overall design: 4 technical replicates were used and later pooled together for the bioinformatic analysis.
Publication Title
Efficient Generation of CA3 Neurons from Human Pluripotent Stem Cells Enables Modeling of Hippocampal Connectivity In Vitro.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Messenger RNAs that are bound to Ago1 is to be transcriptionally or translational suppressed. Therefore the changes in Ago1-associated transcripts indicate the changes of suppression of these genes.
Publication Title
Hypoxia-responsive miRNAs target argonaute 1 to promote angiogenesis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 35 Downloadable Samples
- Illumina HiSeq 2500, Illumina HiSeq 3000
Description
To understand the extent of Smad-mediated gene regulation in the colon, we isolated colon epithelium from Smad4?Lrig1 and from Smad4+ control mice (either mice lacking a CreERT allele and treated with tamoxifen, or mice bearing a CreERT allele but treated with vehicle only) and analyzed the colonic epithelium by RNAseq. The ability of TGFß1 and/or BMP2 to block TNF-mediated induction of Ccl20 from our study suggests that these Smad-mediated pathways may act as gatekeepers for induction of other inflammation-associated genes. To determine if Smad-mediated signaling blocks all or specific subsets of TNF-induced genes, we analyzed both colonocytes and mouse colonoid treated with or without TNF, TGFß1, and BMP2 by RNA seq. Overall design: In total, three RNAseq experiments were performed and three biological replicates were used for each condition: 1. Colon epithelium from Smad4?Lrig1 and from Smad4+ control mice was isolated. Total RNA was isolated from these tissues using RNeasy kit (Qiagen). Processing of RNA using a TruSeq Stranded mRNA sample prep kit was conducted according to the manufacturer's instructions (Illumina, San Diego, CA). 32~37 million 51 base pair single-end reads were generated per sample. 2. Total RNA was isolated from colonocytes treated with or without TNF, TGFß1, and BMP2 using RNeasy kit (Qiagen). Processing of RNA using a TruSeq Stranded mRNA sample prep kit was conducted according to the manufacturer's instructions (Illumina, San Diego, CA). 26~50 million 75 base pair paired-end reads were generated per sample. 3. Total RNA was isolated from mouse colonoid treated with or without TNF, TGFß1, and BMP2 using RNeasy kit (Qiagen). Processing of RNA using a TruSeq Stranded mRNA sample prep kit was conducted according to the manufacturer's instructions (Illumina, San Diego, CA). 50~72 million 75 base pair paired-end reads were generated per sample.
Publication Title
Epithelial Smad4 Deletion Up-Regulates Inflammation and Promotes Inflammation-Associated Cancer.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples