Cutaneous, acral and mucosal subtypes of melanoma were evaluated by whole-genome sequencing, revealing genes affected by novel recurrent mutations to the promoter (TERT, DPH3, OXNAD1, RPL13A, RALY, RPL18A, AP2A1), 5-UTR (HNRNPUL1, CCDC77, PES1), and 3-UTR (DYNAP, CHIT1, FUT9, CCDC141, CDH9, PTPRT) regions. TERT promoter mutations had the highest frequency of any mutation, but neither they nor ATRX mutations, associated with the alternative telomere lengthening mechanism, were correlated with greater telomere length. Genomic landscapes largely reflected ultraviolet radiation mutagenesis in cutaneous melanoma and provided novel insights into melanoma pathogenesis. In contrast, acral and mucosal melanomas exhibited predominantly structural changes, and mutation signatures of unknown aetiology not previously identified in melanoma. The majority of melanomas had potentially actionable mutations, most of which were in components of the mitogen-activated protein kinase and phosphoinositol kinase pathways.
Whole-genome landscapes of major melanoma subtypes.
No sample metadata fields
View SamplesRecent reports have proposed a new paradigm for obtaining mature somatic cell types from fibroblasts without going through a pluripotent state, by briefly expressing canonical iPSC reprogramming factors Oct4, Sox2, Klf4 and c-Myc (abbreviated as OSKM), in cells expanded in lineage differentiation promoting conditions. Here we apply genetic lineage tracing for endogenous Nanog, Oct4 and X chromosome reactivation during OSKM induced trans-differentiation, as these molecular events mark final stages for acquisition of induced pluripotency. Remarkably, the vast majority of reprogrammed cardiomyocytes or neural stem cells derived from mouse fibroblasts via OSKM mediated trans-differentiation were attained after transient acquisition of pluripotency, and followed by rapid differentiation. Our findings underscore a molecular and functional coupling between inducing pluripotency and obtaining “trans-differentiated” somatic cells via OSKM induction, and have implications on defining molecular trajectories assumed during different cell reprogramming methods. Overall design: poly RNA-Seq was measured before, during and after conversion of mouse embryonic fibroblasts to neural stem cells using OSKM trans-differentiation method.
Transient acquisition of pluripotency during somatic cell transdifferentiation with iPSC reprogramming factors.
No sample metadata fields
View SamplesGene expression kinetics for BM-DM from C57BL/6 mouse stimulated with four different TLR ligands poly(I:C), R848, LPS, Pam3CSK4 either singly or in paired combination, for 1 hour, 4 hour, or 8 hour.
Systematic Investigation of Multi-TLR Sensing Identifies Regulators of Sustained Gene Activation in Macrophages.
Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Systematic Investigation of Multi-TLR Sensing Identifies Regulators of Sustained Gene Activation in Macrophages.
Treatment
View SamplesGene expression kinetics for BM-DM from C57BL/6 mice challenged by poly(I:C) , R848, poly(I:C)+R848 examined at 6 time points including 0.5, 1, 2, 4, 8, 12 h.
Systematic Investigation of Multi-TLR Sensing Identifies Regulators of Sustained Gene Activation in Macrophages.
Treatment
View SamplesMonastrol treatment of Leishmania donovani infected macrophages
A member of the Ras oncogene family, RAP1A, mediates antileishmanial activity of monastrol.
Specimen part, Disease, Treatment
View SamplesGene expression in HeLa cells was profiled using Affymetrix gene expression Human HG-U133_Plus_2 array. Transcript signal was mapped against the chromosome coordinates (probe-by-probe basis) using the HG-U133A_2 Annotations CSV file for hg18 build of the human genome provided by Affymetrix.
Genomic study of replication initiation in human chromosomes reveals the influence of transcription regulation and chromatin structure on origin selection.
Cell line
View SamplesThe mammalian innate immune system senses many bacterial stimuli through the toll-like receptor (TLR) family. Activation of the TLR4 receptor by bacterial lipopolysaccharide (LPS) is the most widely studied TLR pathway due to its central role in host responses to gram-negative bacterial infection and its contribution to endotoxemia and sepsis. Here we describe a genome-wide siRNA screen to identify genes regulating the human macrophage TNF- response to LPS. We include a secondary validation screen conducted with six independent siRNAs per gene to facilitate removal of off-target screen hits. We also provide microarray data from the same LPS-treated macrophage cells to facilitate downstream data analysis. These data provide a resource for analyzing gene function in the predominant pathway driving inflammatory cytokine expression in human macrophages.
Genome-wide siRNA screen of genes regulating the LPS-induced TNF-α response in human macrophages.
Specimen part, Cell line
View SamplesThe mammalian innate immune system senses many bacterial stimuli through the toll-like receptor (TLR) family. Activation of the TLR4 receptor by bacterial lipopolysaccharide (LPS) is the most widely studied TLR pathway due to its central role in host responses to gram-negative bacterial infection and its contribution to endotoxemia and sepsis. Here we describe a genome-wide siRNA screen to identify genes regulating the mouse macrophage TNF- and NF-B responses to LPS. We include a secondary validation screen conducted with six independent siRNAs per gene to facilitate removal of off-target screen hits. We also provide microarray data from the same LPS-treated macrophage cells to facilitate downstream data analysis. These data provide a resource for analyzing gene function in the predominant pathway driving inflammatory signaling and cytokine expression in mouse macrophages.
Genome-wide siRNA screen of genes regulating the LPS-induced NF-κB and TNF-α responses in mouse macrophages.
Specimen part, Cell line
View SamplesTo investigate the role of NKX3.1 in prostate differentiation, we employed transcriptome analysis of mouse seminal vesicle (from 15-month-old Nkx3.1+/+ mice); mouse prostate (from 4-month-old Nkx3.1+/+ and Nkx3.1-/- mice); human prostate cells (RWPE1 cells engineered with empty vector (altered pTRIPZ), NKX3.1 wild type over-expression, and NKX3.1 (T164A) mutant over-expression); and tissue recombinants (generated from combining engineered mouse epithelial cells (seminal vesicle epithelial cells or prostate epithelial cells from 2-month-old mice) and rat UGS mesenchymal cells). Mouse tissue or human cells were snap frozen for subsequent molecular analysis.
Identification of an NKX3.1-G9a-UTY transcriptional regulatory network that controls prostate differentiation.
Age, Specimen part, Cell line
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