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SRP181859
Homo sapiens
30 Downloadable Samples
Illumina HiSeq 2000
Description
Constitutive Wnt activation upon loss of Adenoma polyposis coli (APC) acts as main driver of colorectal cancers (CRC). Targeting Wnt signaling has proven difficult because the pathway is crucial for homeostasis and stem cell renewal. To distinguish oncogenic from physiologic Wnt activity, we have performed comprehensive transcriptome and proteome profiling in human colon organoids. Culture in the presence or absence of exogenous ligand allowed us to discriminate receptor-mediated signaling from the effects of CRISPR/Cas9 induced APC loss. We could catalogue two non-overlapping molecular signatures that were stable at distinct levels of stimulation. Newly identified markers for normal colon stem/progenitor cells and adenomas were validated by immunohistochemistry and flow cytometry. We found that oncogenic Wnt signals are associated with good prognosis in tumors of the consensus molecular subtype 2 (CMS2). In contrast, receptor-mediated signaling was linked to CMS4 tumors and poor prognosis. Together, our data represent a valuable resource for biomarkers that allow more precise stratification of Wnt responses in CRC. Overall design: Culturing normal and CRISPR/Cas9 engineered APC mutant isogenic organoid lines in the presence or absence of Wnt-stimulation, followed by transcriptome and proteome profiling allowed for the stratification of physiologic and oncogenic Wnt responses.
Publication Title
Human colon organoids reveal distinct physiologic and oncogenic Wnt responses.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Constitutive Wnt activation upon loss of Adenoma polyposis coli (APC) acts as main driver of colorectal cancers (CRC). Targeting Wnt signaling has proven difficult because the pathway is crucial for homeostasis and stem cell renewal. To distinguish oncogenic from physiologic Wnt activity, we have performed comprehensive transcriptome and proteome profiling in human colon organoids. Culture in the presence or absence of exogenous ligand allowed us to discriminate receptor-mediated signaling from the effects of CRISPR/Cas9 induced APC loss. We could catalogue two non-overlapping molecular signatures that were stable at distinct levels of stimulation. Newly identified markers for normal colon stem/progenitor cells and adenomas were validated by immunohistochemistry and flow cytometry. We found that oncogenic Wnt signals are associated with good prognosis in tumors of the consensus molecular subtype 2 (CMS2). In contrast, receptor-mediated signaling was linked to CMS4 tumors and poor prognosis. Together, our data represent a valuable resource for biomarkers that allow more precise stratification of Wnt responses in CRC. Overall design: Culturing normal and CRISPR/Cas9 engineered APC mutant isogenic organoid lines in the presence or absence of Wnt-stimulation, followed by transcriptome and proteome profiling allowed for the stratification of physiologic and oncogenic Wnt responses.
Publication Title
Human colon organoids reveal distinct physiologic and oncogenic Wnt responses.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 16 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Lactobacilli are probiotics that, among other health promoting effects, have been ascribed immunostimulating and virus preventive properties. Certain lactobacilli species have been shown to possess strong IL-12 inducing properties. As IL-12 production depends on the up-regulation of type I interferons, we hypothesized that the strong IL-12 inducing capacity of L. acidophilus NCFM in murine bone marrow derived DC is caused by an up-regulation of IFN-, which subsequently stimulates the induction of IL-12 and the dsRNA binding toll like receptor (TLR)-3. The expression of the genes encoding IFN-, IL-12, IL-10 and TLR-3 in DC upon stimulation with L. acidophilus NCFM was measured. L. acidophilus NCFM induced a much stronger expression of ifn-, il-12 and il-10 compared to the synthetic dsRNA ligand Poly I:C, whereas the levels of expressed tlr-3 were similar. By the use of whole genome microarray gene expression, we investigated whether other genes related to the viral defence were up-regulated in DC upon stimulation with L. acidophilus NCFM and found that various virus defence related genes, both early and late, were among the strongest up-regulated genes. The IFN- stimulating capability was also detected in another L. acidophilus strain, but was not a property of other probiotic bacteria tested (B. bifidum and E. coli nissle).The IFN- inducing capacity was markedly reduced in TLR-2 -/- DCs, dependent on endocytosis and the major cause of the induction of il-12 and tlr-3 in L. acidophilus NCFM stimulated cells. Collectively, our results reveal that certain lactobacilli trigger the expression of viral defence genes in DC in a TLR-2 manner through induction of IFN- .
Publication Title
Lactobacillus acidophilus induces virus immune defence genes in murine dendritic cells by a Toll-like receptor-2-dependent mechanism.
Sample Metadata Fields
Treatment, Time
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 4000
Description
The overall goal of this study was to clarify the role of MeCP2 in adult cognition. As one of the measures we analyzed gene expression changes associated with MeCP2 loss in the adult hippocampus. The analysis was performed in basal conditions and after exposure to a novel environment. We report gene expression data of mouse adult hippocampal tissue in which MeCP2 has been knockeddown in both conditions. Overall design: Hippocampal mRNA profiles of 3 months old mice after delivery of a control shRNA sequence or a MeCP2-specific shRNA sequence by RNA-seq. Profiles in basal conditions and after (30 minutes) exposure to a novel environment were obtained. Each condition is in quadriplicate.
Publication Title
Adult hippocampal MeCP2 preserves the genomic responsiveness to learning required for long-term memory formation.
Sample Metadata Fields
Specimen part, Cell line, Subject
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