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Project description:Signaling through the thrombospondin-1 receptor CD47 broadly limits cell and tissue survival of stress, but the molecular mechanisms are incompletely understood. We now show that loss of CD47 permits sustained proliferation of primary murine endothelial cells and enables these cells to spontaneously reprogram to form multipotent embryoid bodies. c-Myc, Klf4, Oct4, and Sox2 expression is elevated in CD47-null endothelial cells, in several tissues of CD47- or thrombospondin-1-null mice, and in a human T cell line lacking CD47. CD47 knockdown acutely increases mRNA levels of c-Myc and other stem cell transcription factors in cells and in vivo, whereas CD47 ligation by thrombospondin-1 suppresses c-Myc expression. The inhibitory effects of increasing CD47 levels can be overcome by maintaining c-Myc expression and are absent in cells with dysregulated c-Myc. Thus, CD47 antagonists enable cell self-renewal and reprogramming by overcoming negative regulation of c-Myc and other stem cell transcription factors. To identify gene expression changes associated with CD47 null cells, we compared the gene expression profile of these cells with WT endothelial cell, CD47 null Embryoid bodies cells and an established Embryonic Stem cell line.
2013-07-10 | E-GEOD-43133 | biostudies-arrayexpress
Project description:Intercellular communication is critical for integrating complex signals in multicellular eukaryotes. Vascular endothelial cells and T lymphocytes closely interact during the recirculation and trans-endothelial migration of T cells. In addition to direct cell-cell contact, we show that T cell derived extracellular vesicles can interact with endothelial cells and modulate their cellular functions. Thrombospondin-1 and its receptor CD47 are expressed on exosomes/ectosomes derived from T cells, and these extracellular vesicles are internalized and modulate signaling in both T cells and endothelial cells. Extracellular vesicles released from cells expressing or lacking CD47 differentially regulate activation of T cells induced by engaging the T cell receptor. Similarly, T cell-derived extracellular vesicles modulate endothelial cell responses to vascular endothelial growth factor and tube formation in a CD47-dependent manner. Uptake of T cell derived extracellular vesicles by recipient endothelial cells globally alters gene expression in a CD47-dependent manner. CD47 also regulates the mRNA content of extracellular vesicles in a manner consistent with some of the resulting alterations in target endothelial cell gene expression. Therefore, the thrombospondin-1 receptor CD47 directly or indirectly regulates intercellular communication mediated by the transfer of extracellular vesicles between vascular cells. Treatment with B6H12 antibody inhibited co-immunoprecipitation of EGFR with CD47 and inhibited EGF-induced EGFR tyrosine phosphorylation. B6H12 treatment of bCSC also suppressed asymmetric cell division and cell proliferation and up-regulated caspase 3/7 activity. Correspondingly, caspase-7 cleavage in human breast cancers correlated with CD47 expression. Our data shows that B6H12 specifically targets bCSCs but not differentiated cancer cells, and this CD47 signaling is independent of SIRPα. Three replicates of each condition were generated. Three replicates of each MDA-231 attached cells (differentiated), MDA-231 in suspension cells (bCSC), MDA-231 in suspension cells (bCSC) treated with Control Antibody and MDA-231 in suspension cells (bCSC) treated with B6H12 Antibody.
2016-04-01 | E-GEOD-67966 | biostudies-arrayexpress
Project description:To identify candidate genes regulated by CD47 Affymetrix Human Genome U133 Plus GeneChip 2.0 HCC cell line Huh7 cells with or without CD47 repressed
2014-06-01 | E-GEOD-47563 | biostudies-arrayexpress
Project description:CD47 is a marker of self and a signaling receptor for thrombospondin-1 that is also a membrane
component of extracellular vesicles (EVs) released by various cell types. Previous studies identified CD47-dependent functional effects of EVs on target cells, mediated by delivery of their RNA contents, and enrichment of specific subsets of coding and noncoding RNAs in CD47+ EVs. Here, transcriptomic analyses of EVs released by human and murine cells revealed CD47-dependent enrichment of capped microRNAs and mRNAs. Knockdown or loss of CD47 in wild type Jurkat T cells or treatment with thrombospondin-1 enhanced levels of specific capped-RNAs released in EVs, and reexpressing CD47 in null cells decreased their levels. Mass spectrometry and co-immunoprecipitation identified specific interactions of CD47 with components of the exportin-1/Ran nuclear export complex and its known cargo proteins and between the CD47 cytoplasmic adapter ubiquilin-1 and the exportin-1/Ran complex. Interaction with CD47 was inhibited following alkylation of exportin-1 at Cys528 by leptomycin B. Leptomycin B treatment increased levels of cap-dependent RNAs and their association with exportin-1 in EVs released from wild type but not CD47-deficient cells. These results indicate that CD47
regulates the trafficking of cap-dependent RNAs to EVs through physical interactions with the exportin-1/Ran transport complex. Within the files, lmj1038 represents the control pulldown from CD47- JinB8 cells whereas lmj1039 is the CD47+ pulldown from wild-type Jurkat cells.
2021-03-01 | MSV000086969 | MassIVE
Project description:Elevated CD47 expression in some cancers is associated with decreased survival and limits phagocytic clearance by engaging its counter-receptor SIRPα, but elevated CD47 mRNA expression in human melanomas is associated with improved survival. Gene expression data suggested that recruitment of natural killer (NK) cells, which highly express CD47, into the tumor microenvironment contribute to this correlation. The CD47 ligand thrombospondin-1 inhibited wildtype but not Cd47-/- murine NK cell proliferation and granzyme B and interferon-γ expression in vitro. Cd47-/- NK cells correspondingly showed augmented effector phenotypes. Although, wildtype and Cd47-/- NK cells were equally effective for killing B16 melanoma cells in vitro, Cd47-/- mice exhibited enhanced B16 tumor growth in vivo. Consistent with the human data, tumor-bearing Cd47-/- mice had decreased splenic NK numbers with impaired effector protein expression and elevated exhaustion markers. A pro-apoptotic signature in Cd47-/- NK cells was associated with stress-mediated elevation of mitochondrial proton leak, increased reactive oxygen species and apoptosis. Gene expression profiling identified CD47-dependent transcriptional responses in in NK cells from tumor-bearing mice that regulate systemic NK activation and exhaustion. Treating wildtype mice with a CD47 antibody that blocks thrombospondin-1 binding delayed tumor growth and was associated with increased NK recruitment and increased granzyme B- and interferon-γ levels in intratumoral NK but not CD8+ T cells. Therefore, CD47 in the tumor microenvironment regulates NK-mediated tumor immunity, and therapeutic blockade enhances NK immune function.
2020-04-13 | GSE113876 | GEO
Project description:Signaling through the thrombospondin-1 receptor CD47 broadly limits cell and tissue survival of stress, but the molecular mechanisms are incompletely understood. We now show that loss of CD47 permits sustained proliferation of primary murine endothelial cells and enables these cells to spontaneously reprogram to form multipotent embryoid bodies. c-Myc, Klf4, Oct4, and Sox2 expression is elevated in CD47-null endothelial cells, in several tissues of CD47- or thrombospondin-1-null mice, and in a human T cell line lacking CD47. CD47 knockdown acutely increases mRNA levels of c-Myc and other stem cell transcription factors in cells and in vivo, whereas CD47 ligation by thrombospondin-1 suppresses c-Myc expression. The inhibitory effects of increasing CD47 levels can be overcome by maintaining c-Myc expression and are absent in cells with dysregulated c-Myc. Thus, CD47 antagonists enable cell self-renewal and reprogramming by overcoming negative regulation of c-Myc and other stem cell transcription factors.
2013-07-10 | GSE43133 | GEO
Project description:Intercellular communication is critical for integrating complex signals in multicellular eukaryotes. Vascular endothelial cells and T lymphocytes closely interact during the recirculation and trans-endothelial migration of T cells. In addition to direct cell-cell contact, we show that T cell derived extracellular vesicles can interact with endothelial cells and modulate their cellular functions. Thrombospondin-1 and its receptor CD47 are expressed on exosomes/ectosomes derived from T cells, and these extracellular vesicles are internalized and modulate signaling in both T cells and endothelial cells. Extracellular vesicles released from cells expressing or lacking CD47 differentially regulate activation of T cells induced by engaging the T cell receptor. Similarly, T cell-derived extracellular vesicles modulate endothelial cell responses to vascular endothelial growth factor and tube formation in a CD47-dependent manner. Uptake of T cell derived extracellular vesicles by recipient endothelial cells globally alters gene expression in a CD47-dependent manner. CD47 also regulates the mRNA content of extracellular vesicles in a manner consistent with some of the resulting alterations in target endothelial cell gene expression. Therefore, the thrombospondin-1 receptor CD47 directly or indirectly regulates intercellular communication mediated by the transfer of extracellular vesicles between vascular cells. HuVEC cells were cocultured with exosomes derived either from Jurkat or JinB8 cells culture media. Each condition was done in triplicate. Also, Exosome RNA from Jurkat or JINB8 cells were compared to each other in triplicate.
2014-09-01 | E-GEOD-56825 | biostudies-arrayexpress
Project description:CD47 is an ubiquitously expressed surface molecule that has a significant impact on immune responses. However, its role for antiviral immunity is not fully understood. We can show that CD47 has an inhibitory role in influenza virus defense, since CD47-deficient mice (CD47-/-) display an increased viral clearance during influenza virus infection. This effect is strongly associated with alveolar macrophages, yet the underlying mechanisms are unclear. Thus, to assess the precise impact of CD47 on antiviral action of alveolar macrophages, transcriptional analysis of ex vivo isolated alveolar macrophages from CD47-/- and WT mice were performed isolated 3dpi. Surprisingly, instead of classical antiviral mediators, an increased expression of both hemoglobin α and hemoglobin β was found in CD47 deficient compared to WT alveolar macrophages upon influenza A virus infection. Importantly, antiviral activity of hemoglobin was already shown for other viruses and thus, CD47 might limit influenza virus defense via the regulation of hemoglobin, which could act as a modulator of the antiviral immune response during the infection.
2022-12-09 | GSE201825 | GEO