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SRP142312
Mus musculus
74 Downloadable Samples
NextSeq 500
Description
Single-cell expression profiling is a rich resource of cellular heterogeneity. While profiling every sample under study is advantageous, such workflow is time consuming and costly. We devised CPM - a deconvolution algorithm in which cellular heterogeneity is inferred from bulk expression data based on pre-existing collection of single-cell RNA-seq profiles. We applied CPM to investigate individual variation in heterogeneity of murine lung cells during in vivo influenza virus infection, revealing that the relations between cell quantities and clinical outcomes varies in a gradual manner along the cellular activation process. Validation experiments confirmed these gradual changes along the cellular activation trajectory. Additional analysis suggests that clinical outcomes relate to the rate of cell activation at the early stages of this process. These findings demonstrate the utility of CPM as a mapping deconvolution tool at single-cell resolution, and highlight the importance of such fine cell landscape for understanding diversity of clinical outcomes. Overall design: Lungs gene expression of Collaborative Cross mice taken 48h after the infection with either the influenza virus or PBS.
Publication Title
Cell composition analysis of bulk genomics using single-cell data.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- 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
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In high income countries 90% of the patients achieve complete remission after induction chemotherapy. However, 30-40% of these patients suffer from relapse. These patients face a dismal prognosis, as the majority (>60%) of relapsed patients die within 5 years. As a result, outcome for pediatric acute myeloid leukemia (AML) patients remains poor and has stabilized over the past 15 years. To prevent or better treat relapse of AML is the best option to improve outcome. Despite patient specific differences, most patients do respond to initial therapy. This suggests that at relapse, mechanisms are active that cause the altered response to chemotherapy. Detailed understanding of mechanisms that cause relapse remain largely elusive. To gain insight in the molecular pathways that characterize relapsed AML, we performed genome wide gene expression profiling on paired initial diagnosis and relapsed AML samples of 23 pediatric AML patients. We used pathway analysis to find which molecular pathways are involved in altered gene expression between diagnosis and relapse samples of individual AML patients.
Publication Title
Gene expression profiles associated with pediatric relapsed AML.
Sample Metadata Fields
Disease
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- 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