Filters
Technology
Platform
GSE98384
Homo sapiens
6 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Characterization of a novel OTX2-driven stem cell program in Group 3 and Group 4 medulloblastoma.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Medulloblastoma (MB) is the most common malignant primary pediatric brain cancer. Among the most aggressive subtypes, Group 3 and Group 4 originate from stem/progenitor cells, frequently metastasize, and often display the worst prognosis, yet, as the names imply, we know the least about the molecular mechanisms driving their progression. Here, we show that the transcription factor orthodenticle homeobox 2 (OTX2) promotes self-renewal while inhibiting differentiation in vitro and increases tumor-initiating capacity from MB stem cell populations in vivo. Characterization of the OTX2 regulatory network revealed a novel relationship between OTX2 and genes associated with multiple axon guidance signaling pathways in Group 3 and Group 4 MB stem/progenitor cells. In particular, OTX2 levels were negatively correlated with semaphorin (SEMA) signaling, as expression of 9 SEMA pathway genes is upregulated following OTX2 knockdown with some being potential direct OTX2 targets. Importantly, this negative correlation between OTX2 and SEMA pathway genes was also observed in patient samples, with lower expression of SEMA4D associated with poor outcome in Group 3 and 4 tumors. Functional studies using established and newly derived MB cell lines demonstrated that increased levels of SEMA pathway genes are associated with decreased self-renewal and growth, and that RHO signaling, known to mediate the effects of SEMA genes, is contributing to the OTX2 KD phenotype. Our study provides critical mechanistic insight into the networks controlled by OTX2 in self-renewing MB cells and reveals novel roles for axon guidance genes and their downstream effectors as putative tumor suppressors and therapeutic targets in Group 3 and Group 4 MB.
Publication Title
Characterization of a novel OTX2-driven stem cell program in Group 3 and Group 4 medulloblastoma.
Sample Metadata Fields
Cell line
View Samples- Caenorhabditis elegans
- 12 Downloadable Samples
Illumina HiSeq 4000
Description
Worms that inherited the sperm genome lacking the repressive mark H3K27me3 (K27me3 M+P-) misexpress genes in their germlines when compared to genetically identitical worms that inherited the sperm genome with H3K27me3 (K27me3 M+P+). Overall design: Transcriptome profiles of hermaphrodite germlines from hybrid worms that inherited the sperm genome with H3K27me3 (4 replicates of K27me3 M+P+) vs without H3K27me3 (4 replicates K27me3 M+P-) to compare to 4 replicates of 'wildtype'.
Publication Title
Sperm-inherited H3K27me3 impacts offspring transcription and development in C. elegans.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
The germ lineage is considered to be immortal. In the quest to extend lifespan, a possible strategy is to drive germline traits in somatic cells, to try to confer some of the germ lineage’s immortality on the somatic body. Notably, a study in C. elegans suggested that expression of germline genes in the somatic cells of long-lived daf-2 mutants confers some of daf-2’s longevity. Specifically, mRNAs encoding components of C. elegans germ granules (P granules) were up-regulated in daf-2 mutant worms, and knock-down of individual P-granule and other germline genes in daf-2 young adults modestly reduced their lifespan. We investigated the contribution of a germline program to daf-2’s long lifespan, and also tested if other mutants known to express germline genes in their somatic cells are long-lived. Our key findings are: 1) We could not detect P-granule proteins in the somatic cells of daf-2 mutants by immunostaining or by expression of a P-granule transgene. 2) Whole-genome transcript profiling of animals lacking a germline revealed that germline transcripts are not up-regulated in the soma of daf-2 worms compared to the soma of control worms. 3) Simultaneous removal of multiple P-granule proteins or the entire germline program from daf-2 worms did not reduce their lifespan. 4) Several mutants that robustly express a broad spectrum of germline genes in their somatic cells are not long-lived. Taken together, our findings argue against the hypothesis that acquisition of a germ cell program in somatic cells increases lifespan and contributes to daf-2’s longevity. Overall design: Transcriptome profiles of 3 replicates of sterile daf-2; mes-1 double mutants (experimental) and 3 replicates of sterile mes-1 single mutants (control) grown at 24°C
Publication Title
Reevaluation of whether a soma-to-germ-line transformation extends lifespan in Caenorhabditis elegans.
Sample Metadata Fields
Cell line, Subject
View Samples- Caenorhabditis elegans
- 12 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Here we uncover antagonistic regulation of transcript levels in the germline of Caenorhabditis elegans hermaphrodites. The histone methyltransferase MES-4 marks genes expressed in the germline with methylated Lys36 on histone H3 (H3K36me) and promotes their transcription; MES-4 also represses genes normally expressed in somatic cells and genes on the X chromosomes. The DRM complex, which includes E2F/DP and Retinoblastoma homologs, affects germline gene expression and prevents excessive repression of X-chromosome genes. Using genome-scale analyses of germline tissue, we show that common germline-expressed genes are activated by MES-4 and repressed by DRM, and that MES-4 and DRM co-bind many germline-expressed genes. Reciprocally, MES-4 represses and DRM activates a set of autosomal soma-expressed genes and overall X-chromosome gene expression. Mutations in mes-4 or the DRM subunit lin-54 oppositely skew target transcript levels and cause sterility; a double mutant restores near wild-type transcript levels and germ cell development. Together, yin-yang regulation by MES-4 and DRM ensures transcript levels appropriate for germ cell function, elicits robust but not excessive dampening of X-chromosome-wide transcription, and may poise genes for future expression changes. Our study reveals that conserved transcriptional regulators implicated in development and cancer counteract each other to fine-tune transcript dosage.
Publication Title
Opposing activities of DRM and MES-4 tune gene expression and X-chromosome repression in Caenorhabditis elegans germ cells.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Decidual macrophage populations, CD11cHI and CD11cLO cells were analyzed for expression profiles and unique characteristics.
Publication Title
Two unique human decidual macrophage populations.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Human Genome U133B Array (hgu133b)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Human decidual NK cells from gravid uteri and NK cells from cycling endometrium are distinct NK cell subsets.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Fragmented RNA cocktails from FACS sorted Human decidual NK cell, and peripheral blood CD56Bright and CD56Dim NK cells, previously hybridization to HGU95AV2 chips (Koopman et al J Exp Med. 2003 Oct 20;198(8):1201-1), were stored long term at -80C, thawed and hybridized to HG-U133A arrays.
Publication Title
Human decidual NK cells from gravid uteri and NK cells from cycling endometrium are distinct NK cell subsets.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133B Array (hgu133b), Affymetrix Human Genome U133A Array (hgu133a)
Description
Fragmented RNA cocktails from FACS sorted Human decidual NK cell, and peripheral blood CD56Bright and CD56Dim NK cells, previously hybridization to HGU95AV2 chips (Koopman et al J Exp Med. 2003 Oct 20;198(8):1201-1), were stored long term at -80C, thawed and hybridized to HG-U133B arrays.
Publication Title
Human decidual NK cells from gravid uteri and NK cells from cycling endometrium are distinct NK cell subsets.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human NK cells from the decidua basalis of gravid uteri (dNK) and from cycling endometrium (eNK) of women undergoing hysterectomy were isolated and compared by gene expression profiling using Affymetrix microarrays with probes representing ~47,400 transcripts. Substantial differences indicate that these two types of NK cells represent distinct subsets.
Publication Title
Human decidual NK cells from gravid uteri and NK cells from cycling endometrium are distinct NK cell subsets.
Sample Metadata Fields
Specimen part
View Samples