Stringent regulation of the interferon signaling pathway is essential for maintaining the immune response to pathogens and tumors. The transcription factor STAT1 is a crucial mediator of this response. Here we show that hCAF1/CNOT7 regulates class I and II interferon pathways at different crucial steps. In resting cells hCAF1 can control STAT1 trafficking by interacting with the latent form of STAT1 in the cytoplasm. IFN treatment induces STAT1 release, suggesting that hCAF1 may shield cytoplasmic STAT1 from undesirable stimulation. Consistent, hCAF1 silencing enhances STAT1 basal promoter occupancy associated with increased expression of a subset of STAT1-regulated genes. Consequently, hCAF1 knockdown cells exhibit an increased protection against viral infection and reduced viral replication. Furthermore, hCAF1 participates in the extinction of the IFN signal, through its deadenylase activity, by speeding up the degradation of some STAT1-regulated mRNAs. Since abnormal and unbalanced JAK/STAT activation is associated with immune disorders and cancer, hCAF1 could play a major role in innate immunity and oncogenesis, contributing to tumor escape.
hCAF1/CNOT7 regulates interferon signalling by targeting STAT1.
Cell line
View SamplesLoss of Syk in normal breast cells in vivo and in vitro: gene expression and phenotypic switch to stem-cell like with induction of invadopodia
Tumor suppressor function of Syk in human MCF10A in vitro and normal mouse mammary epithelium in vivo.
Cell line
View SamplesIn animal gonads, 23-30nt long PIWI interacting RNAs (piRNAs) guarantee genome integrity by guiding the sequence specific silencing of selfish genetic elements such as transposons. Two major branches of piRNA biogenesis, namely primary processing and ping-pong amplification, feed into the PIWI clade of Argonaute proteins. Despite our conceptual understanding of piRNA biogenesis, major gaps exist in the mechanistic understanding of the underlying molecular processes as well as in the knowledge of the involved players. Here, we demonstrate an essential role for the female sterility gene shutdown in the piRNA pathway. Shutdown, an evolutionarily conserved co-chaperone of the immunophilin class is the first piRNA biogenesis factor that is essential for all primary and secondary piRNA populations in Drosophila. Based on these findings, we define distinct groups of piRNA biogenesis factors and reveal the core concept of how PIWI family proteins are hard-wired into piRNA biogenesis processes. Overall design: small-RNA libraries from 2 control samples and 7 knock-down samples of D. mel. ovaries and 2 small-RNA profiles from Piwi IP and Aub IP from OSCs.
The cochaperone shutdown defines a group of biogenesis factors essential for all piRNA populations in Drosophila.
Specimen part, Subject
View SamplesThe immortalized human urothelial cell line, UROtsa, was transformed in six parallel cultures with continual passaging in1 M Cd+2 until the cells were able to attain the ability to form colonies in soft agar and subcutaneous tumors in nude mice. The gene expression profiles between cadmium-transformed and control samples were compared and the differentially expressed genes were identified.
Variation of keratin 7 expression and other phenotypic characteristics of independent isolates of cadmium transformed human urothelial cells (UROtsa).
Cell line
View SamplesWith frequent fluctuations in global climate, plants often experience co-occurring dry-wet cycles and pathogen infection and this combination adversely affects plant survival. In the past, some studies indicated that morpho-physiological responses of plants to the combined stress are different from the individual stressed plants. However, interaction of drought stressed or drought recovered plants with pathogen has not been widely studied at molecular level. Such studies are important to understand the defense pathways that operate as part of combined stress tolerance mechanism. In this study, Arabidopsis plants were exposed to individual drought stress (soil drying at 40% FC, D), Pseudomonas syringae pv tomato DC3000 (PStDC3000), infection and their combination. Plants recovered from drought stress were also exposed to PStDC3000. Beside we have also infiltrated P. syringae pv tabaci (PSta, non-host pathogen) individually or in combination with drought stress. Using Affymetrix WT gene 1.0 ST array, global transcriptome profiling of plants leaves under individual drought stress and pathogen infection was compared with their combination. Results implicate that plants exposed to combined drought and pathogen stress experience a new state of stress where each combination of stressor and their timing defines the plant responses and thus should be studied explicitly.
Global Transcriptional Analysis Reveals Unique and Shared Responses in Arabidopsis thaliana Exposed to Combined Drought and Pathogen Stress.
Specimen part
View SamplesMesenchymal 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 SamplesBone-marrow mesenchymal stem cells (MSCs) are plastic adherent cells that can differentiate into various tissue lineages, including osteoblasts, adipocytes and chondrocytes. However, this progenitor property is not shared by all cells within the MSC population. In addition, MSCs vary in their proliferation capacities and expression of markers. Because of heterogeneity of CD146 expression in the MSC population, we compared CD146-/Low and CD146High cells under clonal and non-clonal (sorted MSCs) conditions to determine whether this expression is associated with specific functions. CD146-/Low and CD146High MSCs did not differ in colony-forming unit-fibroblast number, osteogenic and adipogenic differentiation or in vitro hematopoietic supportive activity. However, CD146-/Low clones proliferated slightly but significantly faster than did CD146High clones. In addition, a strong expression of CD146 molecule was associated with a commitment towards a vascular smooth muscle cell lineage with upregulation of calponin-1 expression. Thus, within a bone-marrow MSC population, certain subpopulations characterized by high expression of CD146, are committed toward a vascular smooth muscle cell lineage.
CD146 expression on mesenchymal stem cells is associated with their vascular smooth muscle commitment.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Human decidual NK cells from gravid uteri and NK cells from cycling endometrium are distinct NK cell subsets.
Specimen part
View SamplesFragmented RNA cocktails from FACS sorted Human decidual NK cell, and peripheral blood CD56Bright and CD56Dim NK cells, previously hybridization to HGU95AV2 chips (Koopman et al J Exp Med. 2003 Oct 20;198(8):1201-1), were stored long term at -80C, thawed and hybridized to HG-U133A arrays.
Human decidual NK cells from gravid uteri and NK cells from cycling endometrium are distinct NK cell subsets.
Specimen part
View SamplesFragmented RNA cocktails from FACS sorted Human decidual NK cell, and peripheral blood CD56Bright and CD56Dim NK cells, previously hybridization to HGU95AV2 chips (Koopman et al J Exp Med. 2003 Oct 20;198(8):1201-1), were stored long term at -80C, thawed and hybridized to HG-U133B arrays.
Human decidual NK cells from gravid uteri and NK cells from cycling endometrium are distinct NK cell subsets.
Specimen part
View Samples