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accession-icon GSE54353
Loss of Lkb1 and Pten Leads to Lung Squamous Cell Carcinoma with Elevated Pdl1 Expression
  • organism-icon Mus musculus
  • sample-icon 15 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Loss of Lkb1 and Pten leads to lung squamous cell carcinoma with elevated PD-L1 expression.

Sample Metadata Fields

Specimen part

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accession-icon GSE54351
Loss of Lkb1 and Pten Leads to Lung Squamous Cell Carcinoma with Elevated Pdl1 Expression: Epithelial Cells
  • organism-icon Mus musculus
  • sample-icon 9 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Lung squamous cell carcinoma (SCC) is a deadly disease for which current treatments are inadequate. We demonstrate that bi-allelic inactivation of Lkb1 and Pten in the mouse lung led to SCC that recapitulated the histology, gene expression and microenvironment found in human disease. Lkb1/Pten-null (LP) tumors expressed the squamous markers Krt5, p63 and Sox2, and transcriptionally resembled the basal subtype of human SCC. In contrast to mouse adenocarcinomas, the LP tumors contained immune populations enriched for tumor-associated neutrophils. Sca1+/Ngfr+ fractions were enriched for tumor propagating cells (TPCs) that could serially transplant the disease in orthotopic assays. TPCs in the LP model and Ngfr+ cells in human SCCs highly expressed Pdl1, suggesting a novel mechanism of immune escape for TPCs.

Publication Title

Loss of Lkb1 and Pten leads to lung squamous cell carcinoma with elevated PD-L1 expression.

Sample Metadata Fields

Specimen part

View Samples
accession-icon GSE54352
Loss of Lkb1 and Pten Leads to Lung Squamous Cell Carcinoma with Elevated Pdl1 Expression: Stroma Cells
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Lung squamous cell carcinoma (SCC) is a deadly disease for which current treatments are inadequate. We demonstrate that bi-allelic inactivation of Lkb1 and Pten in the mouse lung led to SCC that recapitulated the histology, gene expression and microenvironment found in human disease. Lkb1/Pten-null (LP) tumors expressed the squamous markers Krt5, p63 and Sox2, and transcriptionally resembled the basal subtype of human SCC. In contrast to mouse adenocarcinomas, the LP tumors contained immune populations enriched for tumor-associated neutrophils. Sca1+/Ngfr+ fractions were enriched for tumor propagating cells (TPCs) that could serially transplant the disease in orthotopic assays. TPCs in the LP model and Ngfr+ cells in human SCCs highly expressed Pdl1, suggesting a novel mechanism of immune escape for TPCs.

Publication Title

Loss of Lkb1 and Pten leads to lung squamous cell carcinoma with elevated PD-L1 expression.

Sample Metadata Fields

Specimen part

View Samples
accession-icon GSE54838
D-2-Hydroxyglutarate produced by mutant IDH2 causes cardiomyopathy and neurodegeneration in mice
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) have been discovered in several cancer types and cause the neurometabolic syndrome D2-Hydroxyglutaric aciduria (D2HGA). The mutant enzymes exhibit neomorphic activity resulting in production of D2- hydroxyglutaric acid (D-2HG). To study the pathophysiological consequences of the accumulation of D2-HG, we generated transgenic mice with conditionally activated IDH2R140Q and IDH2R172K alleles. Global induction of mutant IDH2 expression in adults resulted in dilated cardiomyopathy, white matter abnormalities throughout the central nervous system (CNS), and muscular dystrophy. Embryonic activation of mutant IDH2 resulted in more pronounced phenotypes, including runting, hydrocephalus, and shortened life spanrecapitulating the abnormalities observed in D2HGA patients. The diseased hearts exhibited mitochondrial damage and glycogen accumulation with a concordant upregulation of genes involved in glycogen biosynthesis. Notably, mild cardiac hypertrophy was also observed in nude mice implanted with IDH2R140Q expressing xenografts, suggesting that 2HG may potentially act in a paracrine fashion. Finally, we show that silencing of IDH2R140Q in mice with an inducible transgene restores heart function by lowering 2HG levels. Together, these findings indicate that inhibitors of mutant IDH2 may be beneficial in the treatment of D2HGA and suggest that 2HG produced by IDH mutant tumors has the potential to provoke a paraneoplastic condition.

Publication Title

D-2-hydroxyglutarate produced by mutant IDH2 causes cardiomyopathy and neurodegeneration in mice.

Sample Metadata Fields

Specimen part

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accession-icon GSE29759
The Role of microRNAs in Neural Stem Cell-supported Endothelial Morphogenesis
  • organism-icon Mus musculus
  • sample-icon 24 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

MicroRNA 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.

Publication Title

The role of microRNAs in neural stem cell-supported endothelial morphogenesis.

Sample Metadata Fields

Specimen part, Disease, Treatment

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accession-icon SRP069968
mRNA-seq from Nutlin-3a, doxorubicin, and DMSO treated HCT116 p21-/- cells
  • organism-icon Homo sapiens
  • sample-icon 12 Downloadable Samples
  • Technology Badge IconNextSeq500

Description

We 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.

Publication Title

Integration of TP53, DREAM, MMB-FOXM1 and RB-E2F target gene analyses identifies cell cycle gene regulatory networks.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE140141
Indirect co-cultivation of HepG2 with differentiated THP-1 cells induces AHR signalling and release of pro-inflammatory cytokines.
  • organism-icon Homo sapiens
  • sample-icon 10 Downloadable Samples
  • Technology Badge Icon Affymetrix Clariom S Human array (clariomshuman)

Description

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.

Publication Title

Indirect co-cultivation of HepG2 with differentiated THP-1 cells induces AHR signalling and release of pro-inflammatory cytokines.

Sample Metadata Fields

Treatment

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accession-icon GSE70526
Expression data from plant tissues during incompatible interaction between the rice host and its major pest, the Asian rice gall midge
  • organism-icon Oryza sativa
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Rice Genome Array (rice)

Description

During 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

Publication Title

Metabolic and transcriptomic changes induced in host during hypersensitive response mediated resistance in rice against the Asian rice gall midge.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE6487
Myogenesis MyoD
  • organism-icon Mus musculus
  • sample-icon 30 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

The 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.

Publication Title

MyoD acetylation influences temporal patterns of skeletal muscle gene expression.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE33100
HIF- and non-HIF-Regulated Hypoxic Responses Require the Estrogen-Related Receptor in Drosophila
  • organism-icon Drosophila melanogaster
  • sample-icon 26 Downloadable Samples
  • Technology Badge Icon 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
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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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