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accession-icon GSE17566
Inactivation of Unr results in induction of differentiation of murine ES cells into the primitive endoderm lineage
  • organism-icon Mus musculus
  • sample-icon 15 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Expression 430A Array (moe430a)

Description

Unr (upstream of N-ras) is a cytoplasmic RNA-binding protein with cold shock domains, involved in regulation of messenger RNA stability and translation. To address the biological role of Unr, we inactivated the unr gene by homologous recombination in mice and embryonic stem (ES) cells. Embryos deficient for Unr die at mid-gestation, and the main phenotypic defects observed, growth deficiency and absence of neural tube closure, suggest a role of Unr in the balance proliferation/differentiation during early development. Here, we report that in Unr-null ES cell cultures, we observed a greater proportion of partially differentiated colonies, together with dispersed, refractile cells with stellate morphology, reminiscent of primitive endoderm (PrE) cells. DNA microarray, immunostaining, and RNA analyses revealed that Unr-null ES cells express a set of PrE markers, including the GATA6 transcription factor, a key inducer of PrE. Although Unr-deficient cells did not downregulate the pluripotency regulators Oct4, Nanog and Sox2, they grew more slowly than the wild-type lines, and their clonogenicity was lower. Silencing of Unr by RNA interference in ES E14 (129 genetic background) resulted in similar phenotypic and molecular changes as those observed in unr-/- ES cells (C57Bl/6 background). Finally, we show that ectopic expression of Unr in unr-/- ES cells partially reverses the endoderm-specific gene expression and the differentiation phenotype.

Publication Title

The RNA-binding protein Unr prevents mouse embryonic stem cells differentiation toward the primitive endoderm lineage.

Sample Metadata Fields

Specimen part, Treatment

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accession-icon GSE36525
Expression data from Shh-driven mouse medulloblastoma and control adult wild-type mouse cerellum
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Medulloblastoma is the most common pediatric CNS cancer. In order to identify important molecules important for deregulated tumor cell growth, we use microarray to detail the global gene expression profile in Shh-driven mouse medulloblastomas and determine the most differentially expressed genes compared to the control wild-type cerebellum.

Publication Title

Voltage-gated potassium channel EAG2 controls mitotic entry and tumor growth in medulloblastoma via regulating cell volume dynamics.

Sample Metadata Fields

Age, Specimen part

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accession-icon GSE77816
Expression analysis of WT and Zbtb4 -/- mouse primary fibroblasts
  • organism-icon Mus musculus
  • sample-icon 10 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 2.0 ST Array (mogene20st)

Description

ZBTB4 is a mammalian transcription factor with Zinc fingers and a BTB/POZ domain, which can bind methylated CpGs, as well as certain unmethylated consensus sequences. ZBTB4 is frequently downregulated in human cancers, but it is unclear whether this is a cause or consequence of transformation. To investigate the role of ZBTB4 in normal and pathological conditions, we generated Zbtb4-/- mice

Publication Title

Loss of the Methyl-CpG-Binding Protein ZBTB4 Alters Mitotic Checkpoint, Increases Aneuploidy, and Promotes Tumorigenesis.

Sample Metadata Fields

Specimen part

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accession-icon GSE81964
Norrin-dependent gene expression in murine cerebellar granule neuron progenitors and Patched medulloblastoma
  • organism-icon Mus musculus
  • sample-icon 30 Downloadable Samples
  • Technology Badge IconIllumina MouseWG-6 v2.0 expression beadchip

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation.

Sample Metadata Fields

Specimen part

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accession-icon GSE81962
Norrin-dependent gene expression in cerebellar granule neuron progenitors
  • organism-icon Mus musculus
  • sample-icon 18 Downloadable Samples
  • Technology Badge IconIllumina MouseWG-6 v2.0 expression beadchip

Description

Medulloblastoma (MB), a tumor of the cerebellum, is the most common malignant brain tumor in children. One third of all human MB exhibits a gene expression signature of Sonic hedgehog (Shh) signaling. Hedgehog (Hh) pathway inhibitors have shown efficacy in clinical trials for MB, however, tumors develop resistance to these compounds, highlighting the need to identify additional therapeutic targets for treatment. We have identified a role for Norrin signaling in tumor initiation in the Patched (Ptch) mouse model of MB. Norrin is a secreted factor that functions as an atypical Wnt by binding to the Frizzled4 (Fzd4) receptor on endothelial cells to activate canonical beta-catenin-mediated Wnt signaling pathway. In the cerebellum, activation of Norrin/Fzd4 signaling is required for the establishment and maintenance of the blood brain barrier (BBB). We have identified a role for Norrin signaling in the stroma as a potent tumor inhibitory signal. Inactivation of Norrin in Ptch+/- mice significantly shortens latency and increases MB incidence. This phenotype is associated with an increased frequency of pre-tumor lesions and their conversion to malignancy. In this context, loss of Norrin signalling in endothelial cells is associated with an accelerated transition to a pro-tumor stroma characterized by vascular permeability, inflammation and angiogenic remodelling. Accordingly, loss of Ndp significantly alters the stromal gene expression signature of established Ptch MB.

Publication Title

Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation.

Sample Metadata Fields

Specimen part

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accession-icon GSE81963
Norrin-dependent gene expression in Patched mouse medulloblastoma
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge IconIllumina MouseWG-6 v2.0 expression beadchip

Description

Medulloblastoma (MB), a tumor of the cerebellum, is the most common malignant brain tumor in children. One third of all human MB exhibits a gene expression signature of Sonic hedgehog (Shh) signaling. Hedgehog (Hh) pathway inhibitors have shown efficacy in clinical trials for MB, however, tumors develop resistance to these compounds, highlighting the need to identify additional therapeutic targets for treatment. We have identified a role for Norrin signaling in tumor initiation in the Patched (Ptch) mouse model of MB. Norrin is a secreted factor that functions as an atypical Wnt by binding to the Frizzled4 (Fzd4) receptor on endothelial cells to activate canonical beta-catenin-mediated Wnt signaling pathway. In the cerebellum, activation of Norrin/Fzd4 signaling is required for the establishment and maintenance of the blood brain barrier (BBB). We have identified a role for Norrin signaling in the stroma as a potent tumor inhibitory signal. Inactivation of Norrin in Ptch+/- mice significantly shortens latency and increases MB incidence. This phenotype is associated with an increased frequency of pre-tumor lesions and their conversion to malignancy. In this context, loss of Norrin signalling in endothelial cells is associated with an accelerated transition to a pro-tumor stroma characterized by vascular permeability, inflammation and angiogenic remodelling. Accordingly, loss of Ndp significantly alters the stromal gene expression signature of established Ptch MB.

Publication Title

Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation.

Sample Metadata Fields

Specimen part

View Samples
accession-icon GSE60149
Global hepatic transcript data from fasted male BXD strains on chow or high fat diet
  • organism-icon Mus musculus
  • sample-icon 81 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Transcript data from livers from fasted-state BXD strains on chow or high fat diet

Publication Title

Multilayered genetic and omics dissection of mitochondrial activity in a mouse reference population.

Sample Metadata Fields

Specimen part

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accession-icon GSE70576
EAG2 potassium channel with evolutionarily conserved function as a brain tumor target
  • organism-icon Homo sapiens
  • sample-icon 1 Downloadable Sample
  • Technology Badge Icon Affymetrix Human Gene 2.0 ST Array (hugene20st)

Description

Characterizing the impact of pharmacological and shRNA-mediated silencing of EAG2 in medulloblastoma.

Publication Title

EAG2 potassium channel with evolutionarily conserved function as a brain tumor target.

Sample Metadata Fields

Specimen part, Cell line

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accession-icon GSE63670
Whole genome expression and DNA methylation analysis of matched primary-metastases medulloblastomas
  • organism-icon Homo sapiens
  • sample-icon 5 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 2.0 ST Array (hugene20st), Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Medulloblastoma subgroups remain stable across primary and metastatic compartments.

Sample Metadata Fields

Sex, Age, Specimen part, Subject

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accession-icon GSE63668
Whole genome expression of matched primary-metastases medulloblastomas
  • organism-icon Homo sapiens
  • sample-icon 5 Downloadable Samples
  • Technology Badge IconIllumina HumanMethylation450 BeadChip (HumanMethylation450_15017482), Affymetrix Human Gene 2.0 ST Array (hugene20st)

Description

Affymetrix Human Gene 2.0 ST Array profiling of 9 pairs of matched primary-metastases medulloblastoma samples.

Publication Title

Medulloblastoma subgroups remain stable across primary and metastatic compartments.

Sample Metadata Fields

Sex, Age, Specimen part, Subject

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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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Developed by the Childhood Cancer Data Lab

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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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