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accession-icon GSE33308
Keratinocyte Growth Factor and Dexamethasone Plus Elevated cAMP Levels Synergistically Support Pluripotent Stem Cell Differentiation into Alveolar Epithelial Type II Cells.
  • organism-icon Mus musculus
  • sample-icon 10 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Alveolar epithelial type II (ATII)-like cells can be generated from murine embryonic stem cells (ESCs), although to date, no robust protocols applying specific differentiation factors are established. We hypothesized that the keratinocyte growth factor (KGF), an important mediator of lung organogenesis and primary ATII cell maturation and proliferation, together with dexamethasone, 8-bromoadenosine-cAMP, and isobutylmethylxanthine (DCI), which induce maturation of primary fetal ATII cells, also support the alveolar differentiation of murine ESCs. Here we demonstrate that the above stimuli synergistically potentiate the alveolar differentiation of ESCs as indicated by increased expression of the surfactant proteins (SP-) C and SP-B. This effect is most profound if KGF is supplied not only in the late stage, but at least also during the intermediate stage of differentiation. Our results indicate that KGF most likely does not enhance the generation of (mes)endodermal or NK2 homeobox 1 (Nkx2.1) expressing progenitor cells but rather, supported by DCI, accelerates further differentiation/maturation of respiratory progeny in the intermediate phase and maturation/proliferation of emerging ATII cells in the late stage of differentiation. Ultrastructural analyses confirmed the presence of ATII-like cells with intracellular composite and lamellar bodies. Finally, induced pluripotent stem cells (iPSCs) were generated from transgenic mice with ATII cell-specific lacZ reporter expression. Again, KGF and DCI synergistically increased SP-C and SP-B expression in iPSC cultures, and lacZ expressing ATII-like cells developed. In conclusion, ATII cell-specific reporter expression enabled the first reliable proof for the generation of murine iPSC-derived ATII cells. In addition, we have shown KGF and DCI to synergistically support the generation of ATII-like cells from ESCs and iPSCs. Combined application of these factors will facilitate more efficient generation of stem cell-derived ATII cells for future basic research and potential therapeutic application.

Publication Title

Keratinocyte growth factor and dexamethasone plus elevated cAMP levels synergistically support pluripotent stem cell differentiation into alveolar epithelial type II cells.

Sample Metadata Fields

Specimen part, Treatment

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accession-icon GSE17939
MEK5D-transfected HUVEC
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

We expressed a constitutively active mutant of MEK5 (MEK5D) in human primary endothelial cells (EC) to study the transcriptional and functional responses to Erk5 activation under static conditions.

Publication Title

Erk5 activation elicits a vasoprotective endothelial phenotype via induction of Kruppel-like factor 4 (KLF4).

Sample Metadata Fields

Cell line

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accession-icon SRP021462
Deep sequencing of endogenous mRNA from Caenorhabditis elegans in the presence and absence of arsenite
  • organism-icon Caenorhabditis elegans
  • sample-icon 4 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer IIx

Description

Background: Arsenite is one of the most toxic chemical substances known and is assumed to exert detrimental effects on viability even at lowest concentrations. By contrast and unlike higher concentrations, we here find that exposure to low-dose arsenite promotes growth of cultured mammalian cells. In the nematode C. elegans, low-dose arsenite promotes resistance against thermal and chemical stressors, and extends lifespan of this metazoan, whereas higher concentrations reduce longevity. While arsenite causes a transient increase in reactive oxygen species (ROS) levels in C. elegans, co-exposure to ROS scavengers prevents the lifespan-extending capabilities of arsenite, indicating that transiently increased ROS levels act as transducers of arsenite effects on lifespan, a process known as mitohormesis. The RNA-seq data comprises 2 biological replicates for worms exposed to 100nM Arsenite 48h after L4 and 2 biological replicates of the same age as controls Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de) Overall design: 4 samples: 2 mRNA profiles of C.elegans 48h after L4 exposed to Arsenite; 2 mRNA profiles of C.elegans 48h after L4 as controls (H20). The N2 wild type (var. Bristol) strain was used.

Publication Title

Mitochondrial hormesis links low-dose arsenite exposure to lifespan extension.

Sample Metadata Fields

Specimen part, Treatment, Subject

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accession-icon GSE26410
Inflammation leads to loss of smooth muscle cells but fails to induce invasiveness in a prostate tumor model
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Inflammation has a causal role in many cancers. In prostate cancers, epidemiological data suggest a link between prostatitis and subsequent cancer development, but a proof for this concept in a tumor model has been lacking. A constitutively active version of the IkappaB kinase 2 (IKK2), the molecule activated by a plethora of inflammatory stimuli, was expressed specifically in the prostate epithelium. Signaling of the IKK2/NF-kappaB axis was insufficient for transformation of prostate tissue. However, while PTEN+/- epithelia exhibited intraepithelial neoplasias only recognizable by nuclear alterations, additional IKK2 activation led to an increase in tumor size and formation of cribriform structures and to a fiber increase in the fibroblastic stroma. This phenotype was coupled with inflammation in the prostate gland characterized by infiltration of granulocytes and macrophages. Molecular characterization of the tissues showed a specific loss of smooth muscle markers as well as expression of chemokines attracting immune cells. Isolation of epithelial and stromal cells showed differential chemokine expression by these cells. Correlation studies showed the inflammatory phenotype coupled to loss of smooth muscle in infiltrated glands, but maintenance of the phenotype in glands where inflammation had decreased. Despite the loss of the smooth muscle barrier, tumors were not invasive in a stable genetic background. Data mining revealed that smooth muscle markers are downregulated in human prostate cancers and literature data show that loss of these markers in primary tumors is associated with subsequent metastasis. Our data show that loss of smooth muscle and invasiveness of the tumor are not coupled. Thus, inflammation during early steps of tumorigenesis can lead to increased tumor size and a potential change in the subsequent metastatic potential, but the tumor requires an additional transformation to become a carcinoma.

Publication Title

Persistent inflammation leads to proliferative neoplasia and loss of smooth muscle cells in a prostate tumor model.

Sample Metadata Fields

Age, Specimen part

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accession-icon GSE74297
MALT1 protease activity controls the expression of inflammatory genes in keratinocytes upon Zymosan stimulation
  • organism-icon Homo sapiens
  • sample-icon 3 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 2.0 ST Array (hugene20st)

Description

The protease activity of the paracaspase MALT1 plays an important role in antigen receptor-mediated lymphocyte activation by controlling the activity of the transcription factor NF-kB and is thus essential for the expression of inflammatory target genes.

Publication Title

MALT1 Protease Activity Controls the Expression of Inflammatory Genes in Keratinocytes upon Zymosan Stimulation.

Sample Metadata Fields

Treatment

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accession-icon GSE57200
Expression profile after stable HIF-1a inhibition in gastric cancer cells under normoxic conditions
  • organism-icon Homo sapiens
  • sample-icon 9 Downloadable Samples
  • Technology Badge IconIllumina HumanRef-8 v3.0 expression beadchip

Description

Based on the results of numerous clinical and preclinical analyses, the transcription factor HIF-1a has been identified as an important tumor-promoting factor and is considered to be an attractive target for cancer therapy. To further deconstruct the molecular nature of HIF-1as role in tumorigenesis, we have applied lentiviral shRNA transduction to establish HIF-1a-deficient gastric cancer cells. Interestingly, functional analyses failed to show a significant growth defect of HIF-1a-deficient gastric cancer cells in vitro and in vivo. These observations led us to propose that stable inactivation of HIF-1a resulted in efficient compensation enabling cell growth and, ultimately, tumor progression in a HIF-1a-independent manner. To better understand the mechanisms that control this compensation, we performed transcriptomics of control (scrambled (SCR)) and HIF-1a-deficient (HIF) gastric cancer cells.

Publication Title

Annexin A1 sustains tumor metabolism and cellular proliferation upon stable loss of HIF1A.

Sample Metadata Fields

Specimen part, Cell line

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accession-icon GSE19625
Identification of LPS-inducible genes down-regulated by ubiquinone in human THP-1 cells
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Coenzyme Q10 (CoQ10) is an obligatory element in the respiratory chain and functions as a potent antioxidant of lipid membranes. More recently, anti-inflammatory effects as well as an impact of CoQ10 on gene expression have been observed. To reveal putative effects of Q10 on LPS-induced gene expression, whole genome expression analysis was performed in the monocytic cell line THP-1. 1129 probe sets have been identified to be significantly up-regulated (p < 0.05) in LPS-treated cells when compared to controls. Text mining analysis of the top 50 LPS up-regulated genes revealed a functional connection in the NFB pathway and confirmed our applied in vitro stimulation model. Moreover, 33 LPS-sensitive genes have been identified to be significantly down-regulated by Q10-treatment between a factor of 1.32 and 1.85. GeneOntology (GO) analysis revealed for the Q10-sensitve genes a primary involvement in protein metabolism, cell proliferation and transcriptional processes. Three genes were either related to NFB transcription factor activity, cytokinesis or modulation of oxidative stress. In conclusion, our data provide evidence that Q10 down-regulates LPS-inducible genes in the monocytic cell line THP-1. Thus, the previously described effects of Q10 on the reduction of pro-inflammatory mediators might be due to its impact on gene expression.

Publication Title

Identification of LPS-inducible genes downregulated by ubiquinone in human THP-1 monocytes.

Sample Metadata Fields

Specimen part

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accession-icon SRP174225
Impact of dietary antigen on gene expression of Peyer's patch T cells
  • organism-icon Mus musculus
  • sample-icon 26 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

Transcriptional profiling shows that Peyer´s patch CD4+ T cells from mice kept on dietary antigens are skewed towards a Tfh cell programme. Continous recognition of dietary antigens does not lead to classical signature of exhaustion. Overall design: Examination of conventional and elemental diet on gene expression of PP T cells

Publication Title

Intestinal development and homeostasis require activation and apoptosis of diet-reactive T cells.

Sample Metadata Fields

Specimen part, Cell line, Subject

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accession-icon GSE140882
Targeting chronic NFAT activation with calcineurin inhibitors in diffuse large B-cell lymphoma
  • organism-icon Homo sapiens
  • sample-icon 27 Downloadable Samples
  • Technology Badge IconIllumina HumanHT-12 V4.0 expression beadchip

Description

Diffuse large B-cell lymphoma (DLBCL) represents the most common form of lymphoma. We could show that in DLBCL cell lines the transcription factor NFAT is constitutively activated and drives the survival of a DLBCL subset. Aim of the analysis was to identify NFAT target genes in a NFAT-dependent (HBL-1) or -independent (HT) DLBCL cell line. To block NFAT activity, the DLBCL cells were treated with the calcineurin inhibitor cyclosporin A (CsA) up to 48 h. With this approach, we identified several survival-related NFAT target genes in HBL-1 cells that might explain the toxic effects of calcineurin inhibitors.

Publication Title

Targeting chronic NFAT activation with calcineurin inhibitors in diffuse large B-cell lymphoma.

Sample Metadata Fields

Treatment

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accession-icon GSE23751
In Vitro Transcriptome Analysis of Porcine Plexus Epithelial Cells in Response to Streptococcus suis: Functions of the Choroid Plexus in Antimicrobial Defense
  • organism-icon Sus scrofa
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Porcine Genome Array (porcine)

Description

We used microarrays to detail the global gene expression changes following apical infection of porcine choroid plexus epithelial cells (PCPEC) with Streptococcus suis (S. suis)

Publication Title

In vitro transcriptome analysis of porcine choroid plexus epithelial cells in response to Streptococcus suis: release of pro-inflammatory cytokines and chemokines.

Sample Metadata Fields

Specimen part

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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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