Cell communication within tissues is mediated by multiple paracrine signals including growth factors, which control cell survival and proliferation. Cells and the growth factors they produce and receive constitute a circuit, yet the design features of cell circuits involved in tissue homeostasis are unknown. Here we used computational and experimental approaches to characterize the features of cell circuits based on growth factor exchange between macrophages and fibroblasts, two cell types found in most mammalian tissues. We found that the macrophage-fibroblast cell circuit is stable and robust to perturbations. We employed analytical screening of all possible two-cell circuit topologies and defined the circuit features sufficient for stability, including environmental constraint and negative feedback regulation. Moreover, we discovered that cell-cell contact was essential for the stability of the macrophage-fibroblast circuit. These findings highlight general principles of cell circuit design, and provide a new perspective on quantitative understanding of tissue homeostasis. Overall design: 1 sample of murine embryonic fibroblast and 1 sample murine bone marrow derived macrophages are analyzed for their expression of growth factors and growth factor receptors
Circuit Design Features of a Stable Two-Cell System.
Specimen part, Cell line, Subject
View Samples4-Hydroxynonenal (HNE), a cytotoxic and diffusible electrophile generated by the spontaneous decomposition of oxidized lipids, has a suspected role in neurodegenerative and inflammatory disease processes. In addition to promoting cell death, elevated levels of HNE lead to the engagement of cytoprotective signaling pathways, including the heat shock, antioxidant, DNA damage, and ER stress responses. Activation of the heat shock response, mediated by the transcription factor heat shock factor 1 (HSF1), is critical for maintaining cellular viability in the presence of HNE. Accordingly, silencing HSF1 expression using siRNA enhances the toxicity of HNE. Microarray analysis of samples from control and HSF1-silenced cells was performed to investigate which associated changes in gene could be responsible for the decrease in cellular viability.
HSF1-mediated BAG3 expression attenuates apoptosis in 4-hydroxynonenal-treated colon cancer cells via stabilization of anti-apoptotic Bcl-2 proteins.
No sample metadata fields
View SamplesThe goal of this set of experiments was to identify transcripts that are differentially expressed upon reactivation of NMD in an nmd2::HIS3 strain by galactose-induced expression of the NMD2 gene.
Association of yeast Upf1p with direct substrates of the NMD pathway.
No sample metadata fields
View SamplesEffect of either FLO8 or MSS11 deletion and -overexpression on yeast transcript profiles compared to wild type in laboratory yeast strains 1278b and S288c - also the effect of FLO11 (MUC1) overexpression in the 1278b genetic background
Many Saccharomyces cerevisiae Cell Wall Protein Encoding Genes Are Coregulated by Mss11, but Cellular Adhesion Phenotypes Appear Only Flo Protein Dependent.
No sample metadata fields
View SamplesThe goal of this experiment was to identify transcripts associated with the S. cerevisiae Upf1 protein.
Association of yeast Upf1p with direct substrates of the NMD pathway.
No sample metadata fields
View SamplesGenes regulated in different tumor regions, cells isolated by LCM
Estrogen induces c-Kit and an aggressive phenotype in a model of invasive lobular breast cancer.
Specimen part, Treatment
View SamplesGenome-wide analysis of mRNAs regulated by the nonsense-mediated and 5' to 3' mRNA Decay Pathways in Yeast
Genome-wide analysis of mRNAs regulated by the nonsense-mediated and 5' to 3' mRNA decay pathways in yeast.
Sex
View SamplesTo determine the effects of inactivation of both the nosense-mediated mRNA decay pathway and the general 5' to 3' decay pathway on yeast mRNA decay, we compared the expression profiles of the wild-type, xrn1, xrn1 upf1, xrn1 nmd2, and xrn1 upf3 strains.
Genome-wide analysis of mRNAs regulated by the nonsense-mediated and 5' to 3' mRNA decay pathways in yeast.
Sex
View SamplesTranscription mediated by hypoxia inducible factor (HIF-1) contributes to tumor angiogenesis and metastasis but is also involved in the activation of cell-death pathways and normal physiological processes. Given the complexity of HIF-1 signaling it could be advantageous to target a subset of HIF-1 effectors rather than the entire pathway. We compared the genome-wide effects of three molecules that each interfere with the HIF-1-DNA interaction: a polyamide targeted to the hypoxia response element (HRE), siRNA targeted to HIF-1, and echinomycin, a DNA binding natural product with a similar but less specific sequence preference to the polyamide. The polyamide affects a subset of hypoxia-induced genes that are consistent with the binding site preferences of the polyamide. For comparison, siRNA targeted to HIF-1 and echinomycin each affect the expression of nearly every gene induced by hypoxia. Remarkably, the total number of genes affected by either polyamide or HIF-1 siRNA over a range of thresholds is comparable. The data shows how polyamides can be used to affect a subset of a pathway regulated by a transcription factor. In addition, this study offers a unique comparison of three complementary approaches towards exogenous control of endogenous gene expression.
Modulating hypoxia-inducible transcription by disrupting the HIF-1-DNA interface.
No sample metadata fields
View SamplesThe goal of this experiment is to identify transcripts regulated by Edc3p, an activator of mRNA decapping.
YRA1 autoregulation requires nuclear export and cytoplasmic Edc3p-mediated degradation of its pre-mRNA.
No sample metadata fields
View Samples