Dyskeratosis congenita (DC) is an inherited multi-system disorder, characterized by oral leukoplakia, nail dystrophy, and abnormal skin pigmentation, as well as high rates of bone marrow failure, solid tumors, and other medical problems such as osteopenia. DC and telomere biology disorders (collectively referred to as TBD here) are caused by germline mutations in telomere biology genes leading to very short telomeres and limited proliferative potential of hematopoietic stem cells. We found that skeletal stem cells (SSCs) within the bone marrow stromal cell population (BMSCs, also known as bone marrow-derived mesenchymal stem cells), may contribute to the hematological phenotype.
Molecular profile of clonal strains of human skeletal stem/progenitor cells with different potencies.
Cell line
View SamplesWe investigated the clinical implications of lung developmental transcription factors (TTF-1, NKX2-8, and PAX9) which we recently discovered as cooperating oncogenes activated by way of gene amplification at chromosome 14q13 in lung cancer. Using stable transfectants of human bronchial epithelial cells, RNA expression profiles (signatures) representing activation of the biological pathways defined by each of the three genes were determined and used to risk stratify a non-small cell lung cancer (NSCLC) clinical dataset consisting of ninety-one early stage tumors. Co-activation of the TTF-1 and NKX2-8 pathways identified a cluster of patients with poor survival, representing approximately 20% of patients with early stage NSCLC, whereas activation of individual pathways did not reveal significant prognostic power. Importantly, the poor prognosis associated with co-activation of TTF-1 and NKX2-8 was validated in two other independent clinical datasets. Further, lung cancer cell lines showing co-activation of the TTF-1 and NKX2-8 pathways were shown to exhibit resistance to cisplatin, the standard of care for the treatment of NSCLC. Since TTF-1 and NKX2-8 lack specific inhibitors at the current time, we explored an alternative therapeutic strategy. Using signatures of signaling pathway activation, we identified deregulation of specific oncogenic pathways (Ras and Myc) in the TTF-1/NKX2-8 co-activated cohort.
Characterizing the developmental pathways TTF-1, NKX2-8, and PAX9 in lung cancer.
No sample metadata fields
View SamplesDyskeratosis congenita (DC) is an inherited multi-system disorder, characterized by oral leukoplakia, nail dystrophy, and abnormal skin pigmentation, as well as high rates of bone marrow failure, solid tumors, and other medical problems such as osteopenia. DC and telomere biology disorders (collectively referred to as TBD here) are caused by germline mutations in telomere biology genes leading to very short telomeres and limited proliferative potential of hematopoietic stem cells. We found that skeletal stem cells (SSCs) within the bone marrow stromal cell population (BMSCs, also known as bone marrow-derived mesenchymal stem cells), may contribute to the hematological phenotype.
Bone marrow skeletal stem/progenitor cell defects in dyskeratosis congenita and telomere biology disorders.
Cell line
View SamplesSeedlings of 35 different Arabidopsis thaliana ecotypes were compared. Triplicates were performed of 10 ecotpyes, single arrays of 25 ecotypes.
Diversity of flowering responses in wild Arabidopsis thaliana strains.
Specimen part
View SamplesMultiple Sclerosis (MS) is an immune-mediated chronic inflammatory disease affecting the central nervous system. The cause of MS is not known and the mechanism of IFN-beta, a disease-modifying treatment (DMT) approved for MS, is not well-understood. Oligonucleotide microarrays were used to study gene expression in plasmacytoid denditic cells (pDCs) which are antigen-presenting cells implicated in MS pathogenesis.
Multiple sclerosis-linked and interferon-beta-regulated gene expression in plasmacytoid dendritic cells.
Sex, Age, Specimen part, Disease, Disease stage, Subject
View SamplesTranscripts (mRNA) during amino acid limitation after MEK was inhibited were analyzed.
A mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-dependent transcriptional program controls activation of the early growth response 1 (EGR1) gene during amino acid limitation.
Cell line, Treatment
View SamplesThe transcriptional regulator AmpR controls expression of the AmpC -lactamase in P. aeruginosa and other bacteria. Studies have demonstrated that in addition to regulating ampC expression, AmpR also regulates the expression of the sigma factor AlgT/U and the production of some quorum-sensing regulated virulence factors. In order to understand the ampR regulon, we compared the expression profiles of PAO1 and its isogenic ampR mutant, PAOampR in the presence and absence of sub-MIC -lactam stress. The analysis demonstrates that the ampR regulon is much more extensive than previously thought, with the deletion of ampR affecting the expression of over 300 genes. Expression of an additional 207 genes are affected by AmpR when the cells are exposed to sub-MIC -lactam stress, indicating that the ampR regulon in P. aeruginosa is much more extensive than previously thought.
The regulatory repertoire of Pseudomonas aeruginosa AmpC ß-lactamase regulator AmpR includes virulence genes.
Specimen part
View SamplesWe used microarrays to detail gene expression changes in Hs 294T human melanoma cells after treatment with elesclomol alone, or in combination with paclitaxel, to aide in identifing the mechnism of action of elesclomol.
Elesclomol induces cancer cell apoptosis through oxidative stress.
No sample metadata fields
View SamplesWe used microarrays to detail gene expression changes in Hs 294T human melanoma cells after treatment with elesclomol alone, or in combination with NAC, to aide in identifing the mechnism of action of elesclomol.
Elesclomol induces cancer cell apoptosis through oxidative stress.
No sample metadata fields
View SamplesCells can survive effector caspase (caspase 3/7) activation in response to transient apoptotic stimuli, a process named anastasis. To characterize the molecular events that occur during anastasis, we performed whole transcriptome RNA sequencing of untreated, apoptotic, and recovering cells. We found that anastasis is an active, two-stage program with unique transcriptional profiles in each stage. We also identified 10 genes that specific to the early stage of anastasis. Overall design: 3hr ethanol treatment was used to induce apoptosis in Hela cells. Ethanol was washed away after 3hr treatment to allow cells to recover. Total RNA was prepared from mock-treated cells, ethanol-treated cells and cells after 1hr, 2hr, 3hr, 4hr, 8hr, 12hr recovery, followed by ribosomal RNA depletion. 3 biological replicates were included for each group. Sequencing was done using Ion Proton.
A molecular signature for anastasis, recovery from the brink of apoptotic cell death.
Cell line, Treatment, Subject
View Samples