Periostin participates in different processes involved in connective tissue homeostasis. It is also involved in repairment of damaged tissues. We used the osteoblast murine cell line MC3T3-E1 cell line to show how overexpresion of periostin is able to increase their adhesion properties while diminishing their migration capacity. By differential gene expression we evaluated putative targets involved in those cellular properties.
Role of Periostin in Adhesion and Migration of Bone Remodeling Cells.
Specimen part, Cell line
View SamplesTime-point expression analysis of fractures calluses at 1, 3, and 5 days post-fracture in young and old BALB/c mice.
Identification of novel gene expression in healing fracture callus tissue by DNA microarray.
Age, Specimen part
View SamplesWe analyzed gene expression profiles of myeloma cells belonging to the group of bas prognosis RPMI 8226 and LP1 expressing either the GFP protein or a cyclin D1-GFP fusion protein
Cyclin D1 sensitizes myeloma cells to endoplasmic reticulum stress-mediated apoptosis by activating the unfolded protein response pathway.
Specimen part, Cell line
View SamplesTGF ligands act as tumor suppressors in early stage tumors but are paradoxically diverted into potent prometastatic factors in advanced cancers. The molecular nature of this switch remains enigmatic. We now show that TGF-dependent cell migration, invasion and metastasis are empowered by mutant-p53.
A Mutant-p53/Smad complex opposes p63 to empower TGFbeta-induced metastasis.
No sample metadata fields
View SamplesBefore birth B-cells develop in the fetal liver (FL). Here we show that Gli3 activity in the FL stroma is required for B-cell development. In the Gli3-deficient FL B-cell development was reduced at multiple stages, whereas the Sonic hedgehog (Shh)-deficient FL showed increased B-cell development, and Gli3 functioned to repress Shh transcription. Use of a transgenic Hedgehog (Hh)-reporter mouse showed that Shh signals directly to developing B-cells, and that Hh pathway activation was increased in developing B-cells from Gli3-deficient fetal liver. RNAsequencing confirmed that Hh-mediated transcription is increased in B-lineage cells from Gli3-deficient FL, and showed that these cells expressed reduced levels of B-lineage transcription factors and BCR/pre-BCR-signalling genes. We showed that expression of the master regulators of B-cell development, Ebf1 and Pax5, is reduced in developing B-cells from Gli3-deficient FL and increased in Shh-deficient FL, and that in vitro Shh-treatment or neutralisation can repress or induce their expression respectively. Overall design: Wildtype and Gli3 mutant (Gli3+/- and Gli3-/-) (n=2) embryonic day 17.5 fetal livers were sorted for CD19+B220+ cells. RNA extracted from these cells was sequenced to help understand the transcriptional changes governing B cell development in the Gli3 mutants.
The transcription factor Gli3 promotes B cell development in fetal liver through repression of Shh.
Specimen part, Subject
View SamplesMyelodysplastic syndromes and chronic myelomonocytic leukemia (CMML) are characterized by mutations in epigenetic modifiers and aberrant DNA methylation. DNA methyltransferase inhibitors (DMTis) are used to treat these disorders, but response is highly variable with few means to predict which patients will benefit. To develop a molecular means of predicting response at diagnosis, we examined baseline differences in mutations, DNA methylation, and gene expression in 40 CMML patients responsive and resistant to decitabine (DAC). While somatic mutations did not differentiate responders and non-responders, we were able to identify for the first time 158 differentially methylated regions (DMRs) at baseline between responders and non-responders using next-generation sequencing. These DMRs were primarily localized to non-promoter regions and overlapped with distal regulatory enhancers. Using the methylation profiles, we developed an epigenetic classifier that accurately predicted DAC response at the time of diagnosis. We also found 53 differentially expressed genes between responders and non-responders. Genes up-regulated in responders were enriched in the cell cycle, potentially contributing to effective DAC incorporation. Two chemokines overexpressed in non-responders -- CXCL4 and CXCL7 -- were able to block the effect of DAC on normal CD34+ and primary CMML cells in vitro, suggesting their up-regulation contributes to primary DAC resistance. Overall design: mRNA profiling in bone marrow mononuclear cells (BM MNC) from 14 CMML patients (8 decitabine responders vs. 6 non-responders).
Specific molecular signatures predict decitabine response in chronic myelomonocytic leukemia.
No sample metadata fields
View SamplesInnate immune response is the first line of antiviral defense resulting, in most cases, in pathogen clearance with minimal clinical consequences. Viruses have developed diverse strategies to evade innate immune response and to ensure their survival. Using transmissible gastroenteritis virus (TGEV) as a model, we previously reported that accessory gene 7 counteracts host antiviral response by its association with the catalytic subunit of protein phosphatase 1 (PP1c). A transcriptomic analysis was performed to further investigate the effect of gene 7 absence on the host cell.
Alphacoronavirus protein 7 modulates host innate immune response.
Specimen part, Cell line, Time
View SamplesCyanide is stoichiometrically produced as a co-product of the ethylene biosynthesis pathway, and it is detoxified by the b-cyanoalanine synthase enzyme. The molecular and phenotypical analysis of T-DNA insertional mutants of the mitochondrial b-cyanoalanine synthase CYS-C1 suggests that discrete accumulation of cyanide is not toxic for the plant and does not alter mitochondrial respiration rates, but does act as a strong inhibitor of root hair development. The cys-c1 null allele is defective in root hair formation and accumulates cyanide in root tissues. The root hair defect is phenocopied in wild type plants by the exogenous addition of cyanide to the growth medium and is reversed by the addition of hydroxocobalamin. Hydroxocobalamin not only recovers the root phenotype of the mutant, but also the formation of ROS at the initial step of the root hair tip. Transcriptional profile analysis of the cys-c1 mutant reveals that cyanide accumulation acts as a repressor signal for several genes encoding enzymes involved in cell wall rebuilding and the formation of the root hair tip, as well as genes involved in ethylene signaling and metabolism. Our results demonstrate that mitochondrial b-cyanoalanine synthase activity is essential to maintain a low level of cyanide for proper root hair development.
Mitochondrial beta-cyanoalanine synthase is essential for root hair formation in Arabidopsis thaliana.
Specimen part
View SamplesMultiple Myeloma (MM) is an hematological malignancy. MM cells are resistant to X-ray irradiations. We irradiated RPMI 8226 cancer cells with C-ions, which are more energetic than X-ray irradiations. We found that MM cells, RPMI 8226, are also resistant to C-ion irradiations.
HIF-1α and rapamycin act as gerosuppressant in multiple myeloma cells upon genotoxic stress.
Cell line
View SamplesThe goals of this study are to compare transcriptome profiling (RNA-seq) of patients BM with or without ASXL2 mutations. Overall design: Patient bone marrow mRNA profiles with or without ASXL1/2 mutations were generated by deep sequencing
ASXL2 is essential for haematopoiesis and acts as a haploinsufficient tumour suppressor in leukemia.
Specimen part, Subject
View Samples