The M1 and the M2 macrophage polarization programs (activated by IFN? and IL-4, respectively) lie at the opposite edges of a continuum of activation states but are frequently co-activated during co-infections and in cancer despite controlling divergent functional responses. Whether these two programs are mutually exclusive, how they influence each other, and whether one represents the prevailing response, are all open questions. Co-administration of IFN? and IL-4 exerted complex inhibitory effects over the M1 and M2 programs at the level of both epigenomic and transcriptional changes. Computational data mining and validation analyses revealed the molecular basis of the differential sensitivity of genes and cis-regulatory elements to the antagonistic effects of the opposite stimulus. For instance, while STAT1 and IRF motifs were associated with robust and IL-4-resistant responses to IFN?, their coexistence with binding sites for some auxiliary transcription factors such as AP-1, generated vulnerability to IL-4-mediated inhibition. These data provide a core mechanistic framework for the integration of signals that control macrophage activation and the starting point for understanding macrophage responses in complex environmental conditions Overall design: Analysis of transcriptional and epigenomic changes in mouse macrophages stimulated with different cytokines or their combinations
Opposing macrophage polarization programs show extensive epigenomic and transcriptional cross-talk.
Specimen part, Cell line, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Molecular Aging of Human Liver: An Epigenetic/Transcriptomic Signature.
Sex, Age, Specimen part, Disease
View SamplesGene expression profiling of liver biopsies collected from 33 healthy liver donors ranging from 13 to 90 years old. The Affymetrix HG-U133 Plus 2.0 GeneChip platform was used to evaluate gene-expression.
Molecular Aging of Human Liver: An Epigenetic/Transcriptomic Signature.
Sex, Age, Specimen part, Disease
View SamplesGene expression analysis of purified endothelial cells (Ecs), mesenchymal stem cells (MSCs) and mononuclear cells (MNCs) from wild-type and Flt3-ITD knock-in mice. Overall design: Differentially expressed genes analysis of haematopoietic and niche cell populations from Flt3-ITD mice
Niche-mediated depletion of the normal hematopoietic stem cell reservoir by Flt3-ITD-induced myeloproliferation.
No sample metadata fields
View SamplesWe introduce a microfluidic platform that enables off-chip single-cell RNA-seq after multigenerationa lineage tracking under controlled culture conditions. Overall design: Examination of lineage and cell cycle dependent transcriptional profiles in two cell types
A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages.
Specimen part, Cell line, Subject
View SamplesFacioscapulohumeral dystrophy (FSHD) is one of the most common inherited muscular dystrophies. The causative gene remains controversial and the mechanism of pathophysiology unknown. Here we identify genes associated with germline and early stem cell development as targets of the DUX4 transcription factor, a leading candidate gene for FSHD. The genes regulated by DUX4 are reliably detected in FSHD muscle but not in controls, providing direct support for the model that misexpression of DUX4 is a causal factor for FSHD. Additionally, we show that DUX4 binds and activates LTR elements from a class of MaLR endogenous primate retrotransposons and suppresses the innate immune response to viral infection, at least in part through the activation of DEFB103, a human defensin that can inhibit muscle differentiation. These findings suggest specific mechanisms of FSHD pathology and identify candidate biomarkers for disease diagnosis and progression.
DUX4 activates germline genes, retroelements, and immune mediators: implications for facioscapulohumeral dystrophy.
Specimen part
View SamplesVanin1, a regulator of vitamin B5 metabolism, is expressed by sarcoma tumors. We evaluated its impact on sarcoma growth by using sarcoma cell lines derived from p16p19Vnn1-deficient mice and further transduced with an oncogenic RasV12 oncogene (R tumors) in the presence or not of a catalytically active (VR tumors) or mutated (VdR tumors) Vnn1 isoform.
Vnn1 pantetheinase limits the Warburg effect and sarcoma growth by rescuing mitochondrial activity.
Specimen part, Cell line
View SamplesContext: In many cancers, specific subpopulations of cells appear to be uniquely capable of initiating and maintaining tumors. The strongest support for this cancer stem cell model comes from transplantation assays in immune-deficient mice indicating that human acute myeloid leukemia (AML) is organized as a cellular hierarchy driven by self-renewing leukemia stem cells (LSC). This model has significant implications for the development of novel therapies, but its clinical significance remains unclear.
Association of a leukemic stem cell gene expression signature with clinical outcomes in acute myeloid leukemia.
Disease, Disease stage, Subject
View SamplesPurpose: Investigate the molecular determinants of retinal regeneration in adult vertebrates by analyzing the gene expression profiles of control and post-lesion retina of adult zebrafish, a system that regenerates following injury.
Gene expression profiles of intact and regenerating zebrafish retina.
No sample metadata fields
View SamplesThe goal of this study is to identify, in the head of adult flies, mRNA species whose expresson level are altered by overexpression of the Drosophila RNA-binding protein LARK in CNS neurons.
The LARK RNA-binding protein selectively regulates the circadian eclosion rhythm by controlling E74 protein expression.
No sample metadata fields
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