Mesenchymal stromal cells (MSCs) sense and modulate inflammation and represent potential clinical treatment for immune disorders. However, many details of the bidirectional interaction between MSCs and the innate immune comaprtment are still unsolved. Here we describe an unconventional but functional interaction between pro-inflammatory classically activated macrophages (M1M) and MSCs, with CD54 playing a central role. CD54 was upregulated and enriched specifically at the contact area between M1M and MSCs. Moreover, the specific interaction induced calcium signaling and increased the immunosuppressive capacities of MSCs dependent on CD54 mediation. Our data demonstrate that MSCs can detect an inflammatory microenvironment via a direct and physical interaction with innate immune cells. This finding opens new perspectives for MSC-based cell therapy.
CD54-Mediated Interaction with Pro-inflammatory Macrophages Increases the Immunosuppressive Function of Human Mesenchymal Stromal Cells.
Specimen part
View SamplesIn order to investigate the mechanism whereby TEL-PDGF-beta (ETV6-PDGFRB) interferes with human hematopoietic progenitors proliferation and differentiation, we analyzed the gene expression response downstream this oncogene. CD34+ cells infected with lentivirus coding for TEL-PDGFRb were cultured for 7 days in the absence of cytokines. Using Affymetrix microarrays, we compared gene expression in these cells and in cells treated for 4 h with low dose imatinib (Glivec), a potent PDGFR inhibitor, to switch off TEL-PDGFRb signaling.
ETV6-PDGFRB and FIP1L1-PDGFRA stimulate human hematopoietic progenitor cell proliferation and differentiation into eosinophils: the role of nuclear factor-κB.
Specimen part, Treatment
View SamplesSialic acids on vertebrate cell surfaces mediate many biological roles. Altered expression of certain sialic acid types or their linkages can have prognostic significance in human cancer. A classic but unexplained example is enhanced 2-6-sialylation on N-glycans, resulting from over-expression of the Golgi enzyme -galactoside:2-6-sialyltransferase (ST6Gal-I). Previous data supporting a role for the resulting Sia2-3Gal1-4GlcNAc (Sia6LacNAc) structure in tumor biology were based on in vitro studies in transfected carcinoma cells, in which increased Sia6LacNAc on 1-integrins enhanced their binding to ligands, and stimulated cell motility. Here we examine for the first time the in vivo role of the ST6Gal-I enzyme in the growth and differentiation of spontaneous mammary cancers in mice transgenic for an MMTV-promoter-driven polyoma-middle-T antigen, a tumor in which beta1-integrin function is important for tumorigenesis, and in maintaining the proliferative state of tumor cells. Tumors induced in St6gal1 null animals were more differentiated in comparison to those in the wild-type background, both by histological analysis and by protein expression profiles. Furthermore, we show the St6gal1 null tumors have selectively altered expression of genes associated with focal adhesion signaling, and have decreased phosphorylation of FAK, a downstream target of 1-integrins. This first in vivo evidence for a role of ST6Gal-I in tumor progression was confirmed using a novel approach, which conditionally restored St6gal1 in cell lines derived from the null tumors. These findings indicate a role for ST6Gal-I as a mediator of tumor progression, with its expression causing a less differentiated phenotype, via enhanced 1-integrin function.
alpha 2-6-Linked sialic acids on N-glycans modulate carcinoma differentiation in vivo.
Sex, Age, Specimen part
View SamplesTo understand the molecular differences between adipocytes and their contribution to cell-type specific function, we comprehensively characterised the transcriptomes and DNA methylomes using WGBS of isolated adipocytes from the SAT and VAT from normal weight individuals Overall design: WGBS, RNA-seq, and microarrays were used to study epigenetics and transcriptomics human cancer isolated subcutaneous (abdominal - SA) and vieceral (omental - VA) adipocyte, peripheral blood leukocytes (PBL) and visceral adipose tissue (VAT).
Methylome and transcriptome maps of human visceral and subcutaneous adipocytes reveal key epigenetic differences at developmental genes.
Sex, Specimen part, Subject
View SamplesTo understand the molecular differences between adipocytes and their contribution to cell-type specific function, we comprehensively characterised the transcriptomes and DNA methylomes using WGBS of isolated adipocytes from the SAT and VAT from normal weight individuals Overall design: WGBS, RNA-seq, and microarrays were used to study epigenetics and transcriptomics human cancer isolated subcutaneous (abdominal - SA) and vieceral (omental - VA) adipocyte, peripheral blood leukocytes (PBL) and visceral adipose tissue (VAT).
Methylome and transcriptome maps of human visceral and subcutaneous adipocytes reveal key epigenetic differences at developmental genes.
Sex, Specimen part, Subject
View SamplesExon and expression analysis of HeLa cells after knockdown of SON
Son maintains accurate splicing for a subset of human pre-mRNAs.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genetic programs expressed in resting and IL-4 alternatively activated mouse and human macrophages: similarities and differences.
Specimen part, Disease, Treatment
View SamplesAnalysis of alternative activation of macrophages at gene expression level. The study forms part of a wider study where we compare the effects of IL-4 in different human and mouse macrophages. Our results support the notion that in vitro culture conditions greatly affect the macrophage response to IL-4.
Genetic programs expressed in resting and IL-4 alternatively activated mouse and human macrophages: similarities and differences.
Specimen part, Treatment
View SamplesAnalysis of alternative activation of macrophages at gene expression level. The study forms part of a wider study where we compare the effects of IL-4 in different human and mouse macrophages. Our results support the notion that in vitro culture conditions greatly affect the macrophage response to IL-4.
Genetic programs expressed in resting and IL-4 alternatively activated mouse and human macrophages: similarities and differences.
Specimen part, Treatment
View SamplesOral cancer kills about 1 person every hour each day in the United States and is the 6th most prevalent cancer worldwide. In this study we utilized existing microarray data from a prior oral cancer study to examine the role of chronic pro-inflammatory mediators in oral carcionogenesis by comparing gene expression in oral tumors with adjacent non-tumor oral tissue from the same patient
Deletion of macrophage migration inhibitory factor inhibits murine oral carcinogenesis: Potential role for chronic pro-inflammatory immune mediators.
Disease, Subject
View Samples