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Homo sapiens
18 Downloadable Samples
Illumina HiSeq 2000
Description
Cancer stem cell (CSC) identification relies on transplantation assays of cell sub-populations sorted from fresh tumor samples. Herein, we attempt to bypass limitations of abundant tumor source and predetermined immune selection by in-vivo propagating patient derived xenografts (PDX) from human malignant rhabdoid tumor (MRT), a rare and lethal pediatric neoplasm, to an advanced state in which most cells behave as CSCs. Stemness is then probed by comparative transcriptomics of serial PDXs generating a gene signature of EMT, invasion/motility, metastasis and self-renewal, pinpointing putative MRT CSC markers. The relevance of these putative CSC molecules is analyzed by sorting tumorigenic fractions from early-passaged PDX according to one such molecule, deciphering expression in archived primary tumors and testing the effects of CSC molecule inhibition on MRT growth. Using this platform, we identify ALDH1 and lysyl oxidase (LOX) as relevant targets and provide a larger framework for target and drug discovery in rare pediatric cancers. Overall design: Tumorigenic fractions from early-passaged PDX
Publication Title
In Vivo Expansion of Cancer Stemness Affords Novel Cancer Stem Cell Targets: Malignant Rhabdoid Tumor as an Example.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
PAR-1 is known to be involved in the transition from non-metastatic to metastatic melanoma. We sought to determine the downstream target genes regulated by PAR-1 to determine how PAR-1 is contributing to the metastatic melanoma phenotype.
Publication Title
Protease activated receptor-1 inhibits the Maspin tumor-suppressor gene to determine the melanoma metastatic phenotype.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease and a major health problem in the United States. While the cytokine TGF-ß has been implicated in PDAC development, it can exert bot pro- and anti-tumorigenic effects that are highly context dependent and incompletely understood. To better characterize the responses of neoplastic pancreas cells to TGF-ß, three-dimensional (3D) cultures of KrasG12D-expressing mouse pancreatic epithelial cells were employed. While active exposure to exogenous TGF-ß caused the KrasG12D cells to growth arrest, its subsequent removal allowed the cells to enter a hyper-proliferative, quasi-mesenchymal (QM) and progenitor-like state. This transition was highly stable and maintained by autocrine TGF-ß signaling. Transient pulses of TGF-ß have been observed during pancreatitis, a major risk factor for PDAC, and may therefore serve to convert pre-existing KrasG12D-expressing cells into QM cells. While untreated KrasG12D cells formed simple cysts in vivo, QM cells formed ductal structures resembling human PanINs. Furthermore, markers of the QM state are expressed in human PDAC and are associated with worse outcomes. These data suggest that the QM state plays a role in PDAC development and may selectively contribute to more aggressive PDAC subtypes. This work therefore provides novel molecular insights into both PDAC development and the complex role of TGF-ß in tumorigenesis. Overall design: Three technical replicates per experimental group from one isolate were analyzed by RNA sequencing
Publication Title
Pre-neoplastic pancreas cells enter a partially mesenchymal state following transient TGF-β exposure.
Sample Metadata Fields
Subject
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GSE107088- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Wild-type (WT) miR-378a-3p or edited miR-378a-3p were expressed in SB2 KD-ADAR1 cells to identify the genes regulated by edited miR-378a-3p vs WT miR-378a-3p. PARVA was one of the genes identified to be regulated by edited miR-378a-3p. We demonstrate that this regulation of PARVA is lost in highly metastatic melanoma cells.
Publication Title
A-to-I miR-378a-3p editing can prevent melanoma progression via regulation of PARVA expression.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Background. Multiple myeloma (MM) cells depend on the bone marrow (BM) niche for growth and survival. However, the tumor genes regulated by the niche are largely unknown.
Publication Title
Niche-modulated and niche-modulating genes in bone marrow cells.
Sample Metadata Fields
Disease, Disease stage, Time
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Stimulation of HL60 progenitor cells with either DMSO (1.25% v/v) or atRA (10E-07M) resulted in their differentiation into neutrophils within six days. Gene expression profiles across 12 600 genes were measured for the differentiation processes induced by DMSO and atRA at 0, 2, 4, 8, 12, and 18 h and daily thereafter until day 7 using oligonucleotide DNA microarrays.
Publication Title
Cell fates as high-dimensional attractor states of a complex gene regulatory network.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Gene expression profile (GEP) was analyzed in bone marrow (BM) samples from patients with leukemia or leukemic phase of lymphoma at different time points following aspiration. Among numerous changes in GEP evolved over time a discrete subset of > 60 genes exhibited prompt and sustained switch in expression consistently. Similar results were discovered recently in BM samples from patients with multiple myeloma (GSE36036). GEP was also examined in peripheral blood as well as in BM samples depleted of red blood cells (=WBC) and in cultured cells from some of the patients.
Publication Title
Niche-modulated and niche-modulating genes in bone marrow cells.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Human iPS cells derived from normal and Fragile-X fibroblasts in order to assess the capability of Fragile-X iPS cells to be used as a model for different aspects of Fragile-X syndrome. Microarry analysis used to compare global gene expression between human ES cells, the normal and the mutant iPS cells and the original fibroblasts, to demonstrate that the overall reprogramming process succeeded, and that the FX-iPS cells are fully reprogrammed cells.
Publication Title
Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells.
Sample Metadata Fields
Specimen part, Disease, Cell line
View Samples- Homo sapiens
- 7 Downloadable Samples
- IlluminaHiSeq2500
Description
During activation, T cells integrate multiple signals from APCs and cytokine milieu. The blockade of these signals can have clinical benefits as exemplified by CTLA4-Ig, which blocks interaction of B7 co-stimulatory molecules on APCs with CD28 on T cells. Variants of CTLA4-Ig, abatacept and belatacept are FDA approved as immunosuppressive agents in arthritis and transplantation whereas murine studies suggested that CTLA4-Ig can be beneficial in a number of other diseases. However, detailed analysis of human CD4 cell hyporesponsivness induced by CTLA4-Ig has not been performed. Herein, we established a model to study effect of CTLA4-Ig on the activation of human naïve T cells in a human mixed lymphocytes system. Comparison of human CD4 cells activated in the presence or absence of CTLA4-Ig, showed that co-stimulation blockade during TCR activation does not affect NFAT signaling but results in decreased activation of NF-kB and AP-1 transcription factors followed by profound decrease in proliferation and cytokine production. The resulting T cells become hyporesponsive to secondary activation and, although capable of receiving TCR signals, fail to proliferate or produce cytokines, demonstrating properties of anergic cells. However, unlike some models of T cell anergy, these cells did not possess increased levels of TCR signaling inhibitor CBLB. Rather, the CTLA4-Ig induced hyporesponsiveness was associated with an elevated level of p27kip1 cyclin-dependent kinase inhibitor. Overall design: Time series. Human resting and activated T cell dUTP mRNA-Seq profiles were generated on Illumina HiSeq2500
Publication Title
Functional characterization of human T cell hyporesponsiveness induced by CTLA4-Ig.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Cellular reprogramming from somatic cells to induced pluripotent stem cells (iPSCs) can be achieved through forced expression of the transcription factors Oct4, Klf4, Sox2 and c-Myc (OKSM). These factors, in combination with environmental cues, induce a stable intrinsic pluripotency network that confers indefinite self-renewal capacity on iPSCs. In addition to Oct4 and Sox2, the homeodomain-containing transcription factor Nanog is an integral part of the pluripotency network. Although Nanog expression is not required for the maintenance of pluripotent stem cells, it has been reported to be essential for the establishment of both embryonic stem cells (ESCs) from blastocysts and iPSCs from somatic cells. Here we revisit the role of Nanog in direct reprogramming. Surprisingly, we find that Nanog is dispensable for iPSC formation under optimized culture conditions. We further document that Nanog-deficient iPSCs are transcriptionally highly similar to wild-type iPSCs and support the generation of teratomas and chimeric mice. Lastly, we provide evidence that the presence of ascorbic acid in the culture media is critical for overcoming the previously observed reprogramming block of Nanog knockout cells.
Publication Title
Nanog is dispensable for the generation of induced pluripotent stem cells.
Sample Metadata Fields
Specimen part
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