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GSE30377
Homo sapiens
116 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a), Affymetrix HT Human Genome U133A Array (hthgu133a), Affymetrix Human Genome U133B Array (hgu133b)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Stem cell gene expression programs influence clinical outcome in human leukemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 92 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a), Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
Experiments using xenografts show that some solid tumours and leukemias are organized as cellular hierarchies sustained by cancer stem cells (CSC). Despite promise, the relevance of the CSC model to human disease remains uncertain. Here we show that acute myeloid leukemia (AML) follows a CSC model based on sorting multiple populations from each of 16 primary human AML samples and identifying which contain leukemia stem cells (LSC) using a sensitive xenograft assay. Analysis of gene expression from all functionally validated populations yielded an LSC-specific signature. Similarly, a hematopoietic stem cell (HSC) gene signature was established. Bioinformatic analysis identified a core transcriptional program shared by LSC and HSC, revealing the molecular machinery underlying stemness properties. Both stem cell programs were highly significant independent predictors of patient survival and also found in existing prognostic signatures. Thus, determinants of stemness influence clinical outcome of AML establishing that LSC are clinically relevant and not mere artifacts of xenotransplantation.
Publication Title
Stem cell gene expression programs influence clinical outcome in human leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Human Genome U133B Array (hgu133b)
Description
Experiments using xenografts show that some solid tumours and leukemias are organized as cellular hierarchies sustained by cancer stem cells (CSC). Despite promise, the relevance of the CSC model to human disease remains uncertain. Here we show that acute myeloid leukemia (AML) follows a CSC model based on sorting multiple populations from each of 16 primary human AML samples and identifying which contain leukemia stem cells (LSC) using a sensitive xenograft assay. Analysis of gene expression from all functionally validated populations yielded an LSC-specific signature. Similarly, a hematopoietic stem cell (HSC) gene signature was established. Bioinformatic analysis identified a core transcriptional program shared by LSC and HSC, revealing the molecular machinery underlying stemness properties. Both stem cell programs were highly significant independent predictors of patient survival and also found in existing prognostic signatures. Thus, determinants of stemness influence clinical outcome of AML establishing that LSC are clinically relevant and not mere artifacts of xenotransplantation.
Publication Title
Stem cell gene expression programs influence clinical outcome in human leukemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 5 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
In acute myeloid leukemia (AML), leukemia stem cells (LSCs) play a central role in disease progression and recurrence due to their intrinsic capacity for self-renewal and chemotherapy resistance. Whereas epigenetic regulation balances normal blood stem cell self-renewal and fate decisions, mutation and dysregulation of epigenetic modifiers are now considered fundamental to leukemia initiation and progression. Alterations in miRNA function represent a non-canonical epigenetic mechanism influencing malignant hematopoiesis; however, the function of miRNA in LSC remains undetermined. Here we show that miRNA profiling of fractionated AML populations defines an LSC-specific signature that is highly predictive of patient survival. Gain-of-function genetic analysis demonstrated that miR-126 restrained cell cycle progression, prevented LSC differentiation, and increased LSC self-renewal. miR-126 promoted chemo-resistance, preserving LSC quiescence in part through suppression of the G0-to-G1 gatekeeper, CDK3. Thus, in AML, miRNAs influence patient outcome through post-transcriptional regulation of stemness programs in LSC.
Publication Title
miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Here, we examined the role of intestinal epithelial specific tumor suppressive function of 53. We provide evidence that p53 plays a dual role during carcinogen-induced tumorigenesis. At the initiation stage, p53 controls DNA damage and survival of initiated epithelia. In contrast, at later stages, loss of p53 is associated with the formation of an inflammatory microenvironment that is linked to epithelial mesenchymal transition, invasion and metastasis and the activation of NF-kappaB and Stat3. Thus, we propose a novel p53 controlled tumor suppressive function during the progression stage of colorectal cancer that is independent of its well-established role in cell cycle regulation, apoptosis and senescence.
Publication Title
Loss of p53 in enterocytes generates an inflammatory microenvironment enabling invasion and lymph node metastasis of carcinogen-induced colorectal tumors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 342 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Normal human tissue samples from ten post-mortem donors were processed to generate total RNA, which was subsequently analyzed for gene expression using Affymetrix U133 plus 2.0 arrays. Donor information: Donor 1 - 25 year old male; donor 2 - 38 year old male; donor 3 - 39 year old female; donor 4 - 30 year old male; donor 5 - 35 year old male; donor 6 - 52 year old male; donor 7 - 50 year old female; donor 8 - 48 year old female; donor 9 - 53 year old female; donor 10 - 23 year old female
Publication Title
Gene expression analyses reveal molecular relationships among 20 regions of the human CNS.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 73 Downloadable Samples
Illumina HiSeq 2500
Description
Using fluorescence activated cell sorting, we isolated CD45+, CSF1R-GFP+, F4/80+, Ly6G- mouse lung monocytes and macrophages at 7 days after pneumonectomy procedure. We then used microfluidic single cell RNA-sequencing to transcriptional profile unique myeloid subsets. Using the pneumonectomy dataset, we identified 6 cell groups and 4 gene groups that marked several regenerative macrophage subsets including CCR2+, Ly6C+ monocytes and CD206+, Chil3+ M2-like macrophages. Overall design: individual macrophages 7 days post-pneumonectomy in a B6 CSF1R-GFP mouse
Publication Title
Recruited Monocytes and Type 2 Immunity Promote Lung Regeneration following Pneumonectomy.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 31 Downloadable Samples
- Illumina HiSeq 2500
Description
Using fluorescence activated cell sorting, we isolated CD45+, CSF1R-GFP+, F4/80+, Ly6G- mouse lung monocytes and macrophages at 7 days after sham thoracotomy procedures. We then used microfluidic single cell RNA-sequencing to transcriptional profile unique myeloid subsets. Overall design: After sequencing 31 single cell transcriptomes were analyzed. Hierarcical and k-means clustering reveals several populations of macrophages are present in the lung.
Publication Title
Recruited Monocytes and Type 2 Immunity Promote Lung Regeneration following Pneumonectomy.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 280 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Gene expression profiles from 280 formalin-fixed and paraffin embedded normal and tumor samples of four cancer types
Publication Title
Regulatory T-cell Genes Drive Altered Immune Microenvironment in Adult Solid Cancers and Allow for Immune Contextual Patient Subtyping.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples