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GSE61285
Mus musculus
5 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Ovarian cancer patients are generally diagnosed at stage III/IV, when ascites is common. The volume of ascites positively correlates with the extent of metastasis and negatively with prognosis. Membrane GRP78, a stress-inducible endoplasmic reticulum chaperone which also appears on the plasma membrane (memGRP78) of aggressive cancers, plays a crucial role in the maintenance of embryonic stem cells. Our present study demonstrates that tumor cells isolated from ascites generated by epithelial ovarian cancer (ID8 cells) bearing mice have increased memGRP78 expression compared to ID8 cells in normal culture. We hypothesize that these ascites associated memGRP78+ cells are cancer stem-like cells (CSC) and memGRP78 is functionally important in CSCs. Supporting this hypothesis, we show that memGRP78+ cells isolated from ascites have increased sphere forming and tumor initiating abilities compared to memGRP78- cells. When the tumor microenvironment is recapitulated by adding ascites fluid to cell culture, ID8 cells express more memGRP78 and increased self-renewing ability compared to those cultured in medium alone. Moreover, compared to their counterparts cultured in normal medium, ID8 cells cultured in ascites, or isolated from ascites, show an increased expression of stem cell markers Sca-1, Snail and SOX9. Importantly, antibodies directed against the carboxy (COOH)-terminal domain of GRP78 significantly reduce the self-renewing ability of murine and human ovarian cancer cells pre-incubated with ascites, associated with a decreased phosphorylation of Akt and GSK3, and reduced level of the transcriptional factor Snail. Based on this data, we suggest that memGRP78 is a logical therapeutic target for late stage ovarian cancer.
Publication Title
Syngeneic Murine Ovarian Cancer Model Reveals That Ascites Enriches for Ovarian Cancer Stem-Like Cells Expressing Membrane GRP78.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
Complete polarization of macrophages towards an M1-like proinflammatory and antimicrobial state requires combined action of IFN-? and LPS. Synergistic activation of canonical inflammatory NF-?B target genes by IFN-? and LPS is well appreciated, but less is known about whether IFN-? negatively regulates components of the LPS response, and how this affects polarization. A combined transcriptomic and epigenomic approach revealed that IFN-? selectively abrogates LPS-induced feedback and select metabolic pathways by suppressing TLR4-mediated activation of gene enhancers. In contrast to superinduction of inflammatory genes via enhancers that harbor IRF sequences and bind STAT1, IFN-?-mediated repression targeted enhancers with STAT sequences that bound STAT3. TLR4-activated IFN-?-suppressed enhancers comprised two subsets distinguished by differential regulation of histone acetylation and recruitment of STAT3, CDK8 and cohesin, and were functionally inactivated by IFN-?. These findings reveal that IFN-? suppresses feedback inhibitory and metabolic components of the TLR response to achieve full M1 polarization, and provide insights into mechanisms by which IFN-? selectively inhibits TLR4-induced transcription. Overall design: RNA-seq analysis of transcriptional changes in human macrophages that were cultured with or without IFN-? and then stimulated with LPS
Publication Title
IFN-γ selectively suppresses a subset of TLR4-activated genes and enhancers to potentiate macrophage activation.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 414 Downloadable Samples
- Illumina HiSeq 2500
Description
Normalization of RNA-sequencing data is essential for accurate downstream inference, but the assumptions upon which most methods are based do not hold in the single-cell setting. Consequently, applying existing normalization methods to single-cell RNA-seq data introduces artifacts that bias downstream analyses. To address this, we introduce SCnorm for accurate and efficient normalization of scRNA-seq data. Overall design: Total 183 single cells (92 H1 cells, 91 H9 cells), sequenced twice, were used to evaluate SCnorm in normalizing single cell RNA-seq experiments. Total 48 bulk H1 samples were used to compare bulk and single cell properties. For single-cell RNA-seq, the identical single-cell indexed and fragmented cDNA were pooled at 96 cells per lane or at 24 cells per lane to test the effects of sequencing depth, resulting in approximately 1 million and 4 million mapped reads per cell in the two pooling groups, respectively.
Publication Title
SCnorm: robust normalization of single-cell RNA-seq data.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Gallus gallus
- 203 Downloadable Samples
- Illumina HiSeq 2500
Description
Abstract from Vermillion et al: During vertebrate development, progenitor cells give rise to tissues and organs through a complex choreography that commences at gastrulation. A hallmark event of gastrulation is the formation of the primitive streak, a linear assembly of cells along the anterior-posterior (AP) axis of the developing organism. To examine the primitive streak at a single-cell resolution, we measured the transcriptomes of individual chick cells from the streak or the surrounding tissue (the rest of the area pellucida) in Hamburger-Hamilton stage 4 embryos. The single-cell transcriptomes were then ordered by the statistical method Wave-Crest to deduce both the relative position along the AP axis and the prospective lineage of single cells. The ordered transcriptomes reveal intricate patterns of gene expression along the primitive streak. Overall design: Examination of single-cells of stage 4 chicken embryos.
Publication Title
Spatial patterns of gene expression are unveiled in the chick primitive streak by ordering single-cell transcriptomes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
SPT6, encoded by the SUPT6H in humans and Supt6 in mice, respectively, is a conserved histone chaperone that interacts with RNA polymerase II and participates in transcription elongation. However, the question of how SPT6 comes into play in transcriptional activation upon signaling, particularly in mammalian cells, has remained elusive. We investigated the contribution of SPT6 to interferon beta (IFNbeta) induced transcription in mouse NIH3T3 cells. IFNbeta triggers rapid and high level transcription of many IFN-stimulated genes (ISGs). We report here that SPT6 is recruited to ISGs after IFN stimulation. This recruitment was dependent on the interaction with the methyltransferase, NSD2. Further, siRNA-based SPT6 knockdown reduced levels of ISG activation. RNA-Seq analysis showed that SPT6 knockdown diminished about 50% of ISGs whose induction levels were higher than those unaffected by SPT6 knockdown. Under the tested conditions, SPT6 knockdown did not measurably change expression of constitutively expressed genes. This report highlights that SPT6 is recruited in a stimulus-dependent manner and elicits a major impact on signal induced transcription. Overall design: RNA-seq of NIH3T3 cells.
Publication Title
SPT6 interacts with NSD2 and facilitates interferon-induced transcription.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 85 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Full Title: Multilineage Dysplasia (MLD) in AML correlates with MDS-related cytogenetic abnormalities and a prior history of MDS or MDS/MPN but has no independent prognostic relevance: A comparison of 408 cases classified as AML not otherwise specified or AML with myelodysplasia-related changes
Publication Title
Multilineage dysplasia (MLD) in acute myeloid leukemia (AML) correlates with MDS-related cytogenetic abnormalities and a prior history of MDS or MDS/MPN but has no independent prognostic relevance: a comparison of 408 cases classified as "AML not otherwise specified" (AML-NOS) or "AML with myelodysplasia-related changes" (AML-MRC).
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
By WHO 2008, CEBPA-mutated AML became a provisional subentity, but it remains to be clarified how CEBPAmut AML with multilineage dysplasia (MLD; 50% dysplastic cells in 2-3 lineages) but no other MDS-related feature should be classified. We investigated 108 CEBPAmut AML (15.7-87.6 years) for the impact of MLD and genetic features. MLD-positive patients differed from MLD-negative only by lower mean WBC counts (p=0.004), but not by other blood values, biologic characteristics, cytogenetic risk profiles, or additional molecular markers (NPM1mut, FLT3-ITD/TKD, RUNX1, MLL-PTD, IDH1/2). Biallelic CEBPAmut differed from wild-type-cases by differential expression of 213 genes, but did not differ significantly between MLD-positive/-negative patients. Survival outcomes were improved for females and those <60 years, intermediate versus adverse karyotypes (p=0.021), and for biallelic versus monoallelic/homozygous CEBPAmut (p=0.060) in case of FLT3-ITD-negativity. In contrast, 2-year OS (MLD+: 56.5%; MLD-: 65.5%) and 2-year EFS (MLD+: 13.8 months; MLD-: 16.3 months) did not differ significantly between MLD-positive/-negative patients. By univariable Cox regression analysis, gender, age, WBC count and MRC-cytogenetic risk category only were prognostically relevant for OS, while MLD was irrelevant. Therefore, CEBPAmut AML patients should be characterized only according to mut-status, cytogenetic risk groups, or additional mutations, whereas dysplasia is not relevant for this subtype.
Publication Title
Multilineage dysplasia does not influence prognosis in CEBPA-mutated AML, supporting the WHO proposal to classify these patients as a unique entity.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Interest focuses on genes encoding histone demethylases in hematologic malignancies, such as EZH2 (enhancer of zeste homolog 2). EZH2 mutations were recurrently observed in lymphomas and chronic myeloid malignancies, but data in acute leukemias are limited. We investigated 13 PICALM-MLLT10 (=CALM-AF10) rearranged acute leukemia predominantly of T-lineage (7 m/6 f; 653 years) by deep-sequencing for EZH2mut and identified 3 (23%) EZH2mut carriers: one splice site mutation in exon 14, while two patients had missense mutations in the D1 region of exon 5 which interacts with different DNA methyltransferase genes (but no DNMT3Amut was detected in the 13 PICALM-MLLT10-positive patients).
Publication Title
EZH2 mutations and their association with PICALM-MLLT10 positive acute leukaemia.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 19 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20), Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st), Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
We demonstrate that the induction of three transcription factors (SOX10, OLIG2, NKX6.2) in hiPSC-derived neural progenitor cells (hiPSC-NPC) is sufficient to rapidly generate O4+ oligodendrocytes with an efficiency of 60 to 70% within 28 days.
Publication Title
Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors.
Sample Metadata Fields
Specimen part
View Samples