There is increasing evidence that breast and other cancers originate from and are maintained by a small fraction of stem/progenitor cells with self-renewal properties. Whether such cancer stem/progenitor cells originate from normal stem cells based on initiation of a de novo stem cell program, by reprogramming of a more differentiated cell type by oncogenic insults or both remains unresolved. A major hurdle in addressing these issues is lack of immortal human stem/progenitor cells that can be deliberately manipulated in vitro. We present evidence that normal and human telomerase reverse transcriptase (hTERT)-immortalized human mammary epithelial cells (hMECs) isolated and maintained in DFCI-1 medium retain a fraction with progenitor cell properties. These cells co-express basal, luminal and stem/progenitor cell markers. Clonal derivatives of progenitors co-expressing these markers fall into two distinct types: K5+/K19- (Type I) and K5+/K19+ (Type II). We show that both types of progenitor cells have self-renewal and differentiation ability. Through microarray analysis, we want to identify genes and pathways linked to human mammary epithelial stem/progenitor cell self-renewal and differentiation.
Telomerase-immortalized human mammary stem/progenitor cells with ability to self-renew and differentiate.
Sex, Specimen part
View SamplesWe used microarrays to detail the global programme of gene expression after knockdown of Ecdysoneless in hMECs
The cell cycle regulator ecdysoneless cooperates with H-Ras to promote oncogenic transformation of human mammary epithelial cells.
Specimen part, Cell line
View SamplesAda3 (alteration/deficiency in activation) is a transcriptional adaptor that forms a core structural component of multiple HAT complexes. In order to gain insights into physiological roles of Ada3, we made a conditional knockout mouse for Ada3 which was early embryonic lethal. Deletion of Ada3 in MEFs by using Adenovirus-Cre showed changes in global histone acetylation.
Mammalian alteration/deficiency in activation 3 (Ada3) is essential for embryonic development and cell cycle progression.
Specimen part
View SamplesAcute myeloid leukemia (AML) continues to have the lowest survival rates of all leukemias. Therefore, new therapeutic strategies are urgently needed to improve clinical outcomes for AML patients. Here, we report a novel role for Wilms’ tumor 1-associated protein (WTAP) in pathogenesis of AML. We have performed RNA-Seq in K562 cells with knockdown of WTAP to ascertain which genes it regulates. Overall design: We have 2 replicates of total RNA for K562 cells and 2 replicates with WTAP knocked down
WTAP is a novel oncogenic protein in acute myeloid leukemia.
Subject
View SamplesTo normalize transcriptome data we combined total RNA isolated from 10^6 resting or activated B cells with 1 µl of 1/10 dilution of Ambion’s ERCC RNA Spike-in Mix (92 mRNA standards). mRNA was then isolated and processed following Illumina’s RNA-seq protocol v2.
Global regulation of promoter melting in naive lymphocytes.
Specimen part, Cell line
View SamplesAtf1 was overexpressed in wt S. pombe cells for 24 hours and gene expression changes were analysed
Genome wide transcription profiling reveals a major role for the transcription factor Atf1 in regulation of cell division in Schizosaccharomyces pombe.
No sample metadata fields
View SamplesMaintaining cell fate relies on robust mechanisms that prevent the differentiation of specified cells into other cell types. This is especially critical during embryogenesis, when extensive cell proliferation, patterning and migration events take place. Here we show that vertebrate primordial germ cells (PGCs) are protected from reprogramming into other cell types by the RNA-binding protein Dead end (Dnd). PGCs knocked down for Dnd lose their characteristic morphology and adopt that of various somatic cell types. Concomitantly, they gain a gene expression profile reflecting differentiation into cells of different germ layers, in a process that we could direct by expression of specific cell-fate determinants. Importantly, we visualized these events within live zebrafish embryos, which provide temporal information regarding cell reprogramming. Our results shed light on the mechanisms controlling germ cell fate maintenance and are relevant for the formation of teratoma, a tumor class composed of cells from more than one germ layer. Overall design: Transcriptome profiling of 13hpf sorted germ cells of zebrafish embryos injected with either control or dead end Morpholino
The Vertebrate Protein Dead End Maintains Primordial Germ Cell Fate by Inhibiting Somatic Differentiation.
Specimen part, Cell line, Subject
View SamplesTumors that show evidence of epithelial to mesenchymal transition (EMT) have been associated with metastasis, drug resistance, and poor prognosis. EMT may alter the molecular requirements for growth and survival in different contexts, but the underlying mechanisms remain incomplete. Given the heterogeneity along the EMT spectrum between and within tumors it is important to define the requirements for growth and survival in cells with an epithelial or mesenchymal phenotype to maximize therapeutic efficacy.
Epithelial-to-mesenchymal transition rewires the molecular path to PI3K-dependent proliferation.
Specimen part, Cell line, Treatment
View SamplesAllyl alcohol is a highly toxic industrial chemical used as a synthetic substrate, and as an herbicide in agriculture. It is evident that Allyl alcohol is metabolized by alcohol dehydrogenases (ADH) to the highly toxic Acrolein. Acrolein is a simple unsaturated aldehyde, ubiquitous environmental pollutant, endogenous metabolite and major constituent of cigarette smoke. Acrolein is highly electrophilic in nature and has strong reactivity towards nucleophiles present in cell such as amino acids, proteins and DNA.
Molecular cytotoxicity mechanisms of allyl alcohol (acrolein) in budding yeast.
No sample metadata fields
View SamplesSpaceflight results in a number of adaptations to skeletal muscle, including atrophy and shifts towards faster muscle fiber types. To identify changes in gene expression that may underlie these adaptations, microarray expression analysis was performed on gastrocnemius from mice flown on the STS-108 shuttle flight (11 days, 19 hours) versus mice maintained on earth for the same period. Additionally, to identify changes that were due to unloading and reloading, microarray analyses were conducted on calf muscle from ground-based mice subjected to hindlimb suspension (12 days) and mice subjected to hindlimb suspension plus a brief period of reloading (3.5 hours) to simulate the time between landing and sacrifice of the spaceflight mice.
Effects of spaceflight on murine skeletal muscle gene expression.
No sample metadata fields
View Samples