Maintaining 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 SamplesThere 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 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 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 SamplesThis SuperSeries is composed of the SubSeries listed below.
Protective role of IL-6 in vascular remodeling in Schistosoma pulmonary hypertension.
Sex, Specimen part, Disease, Disease stage, Treatment
View SamplesRationale: Schistosomiasis is one of the most common causes of pulmonary arterial hypertension worldwide, but the pathogenic mechanism by which the host inflammatory response contributes to vascular remodeling is unknown. We sought to identify signaling pathways that play protective or pathogenic roles in experimental Schistosoma-induced pulmonary vascular disease by whole-lung transcriptome analysis. Methods: Wildtype mice were experimentally exposed to S. mansoni ova by intraperitoneal sensitization followed by tail vein augmentation, and the phenotype assessed by right ventricular catheterization and tissue histology, RNA and protein analysis. Whole-lung transcriptome analysis by microarray and RNA sequencing was performed, the latter analyzed using 2 bioinformatic methods. Functional testing of the candidate IL-6 pathway was determined using IL6-knockout mice and the STAT3 inhibitor STI-201. Results: Wild-type mice exposed to S. mansoni had increased right ventricular systolic pressure and thickness of the pulmonary vascular media. Whole lung transcriptome analysis identified the IL6-STAT3-NFATc2 pathway as being upregulated, which was confirmed by PCR and immunostaining of lung tissue from S. mansoni-exposed mice and patients who died of the disease. Mice lacking IL6 or treated with STI-201 developed pulmonary hypertension associated with significant intima remodeling after exposure to S. mansoni. Conclusions: Whole lung transcriptome analysis identified upregulation of the IL6-STAT3-NFATc2 pathway, and IL6 signaling was found to be protective against Schistosoma-induced intimal remodeling.
Protective role of IL-6 in vascular remodeling in Schistosoma pulmonary hypertension.
Sex, Specimen part, Disease, Disease stage, Treatment
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
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