A prevalent hypothesis for the cell-to-cell coordination of the phenomena of early development is that a defined mixture of different mRNA species at specific abundances in each cell determines fate and behavior. With this dataset we explore this hypothesis by quantifying the abundance of every mRNA species in every individual cell of the early C. elegans embryo, for which the exact life history and fate is precisely documented. Overall design: Embryos of the 1-, 2-, 4-, 8- and 16-cell stage were dissected into complete sets of single cells, and each cell from each set was sequenced individually using SMARTer technology. 5-9 replicates were generated for each stage. Most cell identities were unknown upon sequencing, but were deduced from by their transcriptomes post hoc.
A Transcriptional Lineage of the Early C. elegans Embryo.
Specimen part, Subject
View SamplesExpression of the MT1-MMP gene induces a significant upregulation of of oncogenes and tumorignenic genes in 184B5-MT1 cells.
Membrane type-1 matrix metalloproteinase confers aneuploidy and tumorigenicity on mammary epithelial cells.
Cell line
View SamplesMetastasis depends on the ability of tumor cells to establish a relationship with the newly seeded host tissue that is conducive to their survival and proliferation. Recent evidence suggests that tumor cells regulate their own dissemination by preparing permissive metastatic niches within host tissues. However, the factors that are implicated in rendering tissues permissive for metastatic tumor growth have yet to be fully elucidated. Breast tumors arising during pregnancy display highly aggressive behaviour and early metastatic proclivity, raising the possibility that pregnancy may constitute a physiological condition of permissiveness for tumor dissemination. We show that during murine gestation, both the rate and degree of metastatic tumor growth are enhanced irrespective of tumor type and that decreased natural killer (NK) cell activity is responsible for the observed increase in experimental metastasis. We identify gene expression changes in pregnant mouse lung and liver that bear striking similarity with reported pre-metastatic niche signatures and several of the up-regulated genes are indicative of myeloid-cell infiltration. We provide evidence, that CD11b+ Gr-1+ myeloid-derived suppressor cells accumulate in pregnant mice and exert an inhibitory effect on NK cell activity, thereby enhancing metastatic tumor growth. MDSC have never been evoked in the context of pregnancy and our observations suggest that they may represent a further shared mechanism of immune suppression occurring during gestation and tumor growth.
Myeloid-derived suppressor cells are implicated in regulating permissiveness for tumor metastasis during mouse gestation.
Specimen part
View SamplesIn order to obtain a global picture regarding regulation of p53 in liver cells we used HepG2 hepatoma cells.We created two isogenic sub-cultures of HepG2 cells with altered expression of p53.
Chemotherapeutic agents induce the expression and activity of their clearing enzyme CYP3A4 by activating p53.
Specimen part, Cell line
View SamplesWe successfully sequenced and annotated more than 400 cells from child, adult control, type 1 diabetes and type 2 diabetes donors. We detect donor-type specific transcript variation. We also report that cells from child donors have less defined gene signature. Cells from type 2 diabetes donors resemble juvenile cells in gene expression. Overall design: Cells from three adult controls (56, 74, 92), one donor with type 1 diabetes (91), two donors with type 2 diabetes (75, 143), and two child donors (40, 72) were sequenced. Numbers in parathesis indicates number of cells sequenced.
Single-Cell Transcriptomics of the Human Endocrine Pancreas.
Specimen part, Subject
View SamplesRecently, a frequent chromosomal aberration fusing Androgen regulated TMPRSS2 promoter and the ERG gene (T/ERG) was discovered in prostate cancer. Several studies demonstrated cooperation between the T/ERG and other defective pathways in cancer progression however, the biological mechanism by which the T/ERG operates is yet to be determined. Using immortalized prostate epithelial cells (EP) model we were able to show that EP with the combination of androgen receptor(AR) and T/ERG(EP-AR T/ERG cell line) demonstrate an Epithelial to Mesenchymal Transition (EMT) manifested by a mesenchyme-like morphological appearance and behavior.
TMPRSS2/ERG promotes epithelial to mesenchymal transition through the ZEB1/ZEB2 axis in a prostate cancer model.
Specimen part, Cell line
View SamplesCancer 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
In Vivo Expansion of Cancer Stemness Affords Novel Cancer Stem Cell Targets: Malignant Rhabdoid Tumor as an Example.
Subject
View SamplesEffect of the overexpression of the oncogenic form of the Vav2 protein in the NIH3T3 cell line under serum deprivation conditions. oncovav2-transformed NIH3T3 cells grown in serum-deprived medium (Vav2SD) are compared to the parental NIH3T3 controls under the same growth conditions (ContSD). Vav2SD cells are also compared to the oncovav2-transformed NIH3T3 cells growing exponentially and the NIH3T3 growing exponentially.
Microarray analysis of gene expression with age in individual nematodes.
Cell line
View SamplesWe conducted a proof-of-concept experiment to explore the possibility of using gene expression-based high throughput screening (GE-HTS) to find inhibitors of a signaling cascade, using platelet derived growth factor receptor (PDGFR) signaling as the example.
Gene expression-based screening for inhibitors of PDGFR signaling.
No sample metadata fields
View SamplesGlial progenitor cells comprise the most abundant population of progenitor cells in the adult human brain. They are responsible for CNS remyelination, and likely contribute to the astrogliotic response to brain injury and degeneration as well. Adult human GPCs are biased to differentiate as oligodendrocytes and elaborate new myelin, and yet they retain multilineage plasticity, and can give rise to neurons as well as astrocytes and oligodendrocytes once removed from the adult parenchymal environment. GPCs retain strong mechanisms for cell-autonomous self-renewal, and yet both their phenotype and fate may be dictated by their microenvironment. Using the transcriptional profiles of acutely isolated GPCs, we have begun to understand the operative ligand-receptor interactions involved in these processes, and have identified several key signaling pathways by which adult human GPCs may be reliably instructed to either oligodendrocytic or astrocytic fate. In addition, we have noted significant differences between the expressed genes and dominant signaling pathways of fetal and adult human GPCs, as well as between rodent and human GPCs. The latter data in particular call into question therapeutic strategies predicated solely upon data obtained using rodents, while perhaps highlighting the extent to which evolution has been attended by the phylogenetic modification of glial phenotype and function.
Fate determination of adult human glial progenitor cells.
Specimen part, Subject
View Samples