20 results on '"Victorero G"'
Search Results
2. Gene expression profiling during thymus ontogeny and its association with TCRV beta 8.1-D beta 2.1 rearrangements of inbred mouse strains
- Author
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Espanhol, AR, Macedo, C, Junta, CM, Cardoso, RS, Victorero, G, Loriod, Béatrice, NGuyen, C, Jordan, B, Passos, GAS, Technologies avancées pour le génôme et la clinique (TAGC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
[SDV]Life Sciences [q-bio] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience; no abstract
- Published
- 2003
- Full Text
- View/download PDF
3. Chromosomal location of the human immunoglobulin lambda variable 8 (IGLV8) gene family outside the major lambda locus on chromosome 22q11.2
- Author
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Queiroz, R. G. P., Carrier, A., Victorero, G., Jordan, B., and Passos, G. A. S.
- Published
- 1997
- Full Text
- View/download PDF
4. Genomic organization and the tissue distribution of alternatively spliced isoforms of the mouse Spatial gene
- Author
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Mattei Marie-Geneviève, Victorero Geneviève, Saade Murielle, Granjeaud Samuel, Puthier Denis, Irla Magali, and Nguyen Catherine
- Subjects
Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background The stromal component of the thymic microenvironment is critical for T lymphocyte generation. Thymocyte differentiation involves a cascade of coordinated stromal genes controlling thymocyte survival, lineage commitment and selection. The "Stromal Protein Associated with Thymii And Lymph-node" (Spatial) gene encodes a putative transcription factor which may be involved in T-cell development. In the testis, the Spatial gene is also expressed by round spermatids during spermatogenesis. Results The Spatial gene maps to the B3-B4 region of murine chromosome 10 corresponding to the human syntenic region 10q22.1. The mouse Spatial genomic DNA is organised into 10 exons and is alternatively spliced to generate two short isoforms (Spatial-α and -γ) and two other long isoforms (Spatial-δ and -ε) comprising 5 additional exons on the 3' site. Here, we report the cloning of a new short isoform, Spatial-β, which differs from other isoforms by an additional alternative exon of 69 bases. This new exon encodes an interesting proline-rich signature that could confer to the 34 kDa Spatial-β protein a particular function. By quantitative TaqMan RT-PCR, we have shown that the short isoforms are highly expressed in the thymus while the long isoforms are highly expressed in the testis. We further examined the inter-species conservation of Spatial between several mammals and identified that the protein which is rich in proline and positive amino acids, is highly conserved. Conclusions The Spatial gene generates at least five alternative spliced variants: three short isoforms (Spatial-α, -β and -γ) highly expressed in the thymus and two long isoforms (Spatial-δ and -ε) highly expressed in the testis. These alternative spliced variants could have a tissue specific function.
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- 2004
- Full Text
- View/download PDF
5. Gene expression profiling in blood from cerebral malaria patients and mild malaria patients living in Senegal.
- Author
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Thiam A, Sanka M, Ndiaye Diallo R, Torres M, Mbengue B, Nunez NF, Thiam F, Diop G, Victorero G, Nguyen C, Dieye A, and Rihet P
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- Adolescent, Adult, Aged, Child, Child, Preschool, Cluster Analysis, Female, Glycogen Synthase Kinase 3 beta genetics, Humans, Infant, Malaria, Cerebral blood, Malaria, Cerebral genetics, Male, Middle Aged, Protein Interaction Maps genetics, Senegal, Severity of Illness Index, Signal Transduction, Transcription Factor RelA genetics, Young Adult, Malaria, Cerebral pathology, Transcriptome genetics
- Abstract
Background: Plasmodium falciparum malaria remains a major health problem in Africa. The mechanisms of pathogenesis are not fully understood. Transcriptomic studies may provide new insights into molecular pathways involved in the severe form of the disease., Methods: Blood transcriptional levels were assessed in patients with cerebral malaria, non-cerebral malaria, or mild malaria by using microarray technology to look for gene expression profiles associated with clinical status. Multi-way ANOVA was used to extract differentially expressed genes. Network and pathways analyses were used to detect enrichment for biological pathways., Results: We identified a set of 443 genes that were differentially expressed in the three patient groups after applying a false discovery rate of 10%. Since the cerebral patients displayed a particular transcriptional pattern, we focused our analysis on the differences between cerebral malaria patients and mild malaria patients. We further found 842 differentially expressed genes after applying a false discovery rate of 10%. Unsupervised hierarchical clustering of cerebral malaria-informative genes led to clustering of the cerebral malaria patients. The support vector machine method allowed us to correctly classify five out of six cerebral malaria patients and six of six mild malaria patients. Furthermore, the products of the differentially expressed genes were mapped onto a human protein-protein network. This led to the identification of the proteins with the highest number of interactions, including GSK3B, RELA, and APP. The enrichment analysis of the gene functional annotation indicates that genes involved in immune signalling pathways play a role in the occurrence of cerebral malaria. These include BCR-, TCR-, TLR-, cytokine-, FcεRI-, and FCGR- signalling pathways and natural killer cell cytotoxicity pathways, which are involved in the activation of immune cells. In addition, our results revealed an enrichment of genes involved in Alzheimer's disease., Conclusions: In the present study, we examine a set of genes whose expression differed in cerebral malaria patients and mild malaria patients. Moreover, our results provide new insights into the potential effect of the dysregulation of gene expression in immune pathways. Host genetic variation may partly explain such alteration of gene expression. Further studies are required to investigate this in African populations.
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- 2019
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6. Sperm mRNAs and microRNAs as candidate markers for the impact of toxicants on human spermatogenesis: an application to tobacco smoking.
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Metzler-Guillemain C, Victorero G, Lepoivre C, Bergon A, Yammine M, Perrin J, Sari-Minodier I, Boulanger N, Rihet P, and Nguyen C
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- Humans, Male, Spermatozoa metabolism, Tobacco Products, MicroRNAs metabolism, RNA, Messenger metabolism, Smoking, Spermatogenesis drug effects, Spermatozoa drug effects
- Abstract
Spermatozoa contain a complex population of RNAs including messenger RNAs (mRNAs) and small RNAs such as microRNAs (miRNA). It has been reported that these RNAs can be used to understand the mechanisms by which toxicological exposure affects spermatogenesis. The aim of our study was to compare mRNA and miRNA profiles in spermatozoa from eight smokers and eight non-smokers, and search for potential relationships between mRNA and miRNA variation. All men were selected based on their answers to a standard toxic exposure questionnaire, and sperm parameters. Using mRNA and miRNA microarrays, we showed that mRNAs from 15 genes were differentially represented between smokers and non-smokers (p<0.01): five had higher levels and 10 lower levels in the smokers. For the microRNAs, 23 were differentially represented: 16 were higher and seven lower in the smokers (0.004≤p<0.01). Quantitative RT-PCR confirmed the lower levels in smokers compared to non-smokers for hsa-miR-296-5p, hsa-miR-3940, and hsa-miR-520d-3p. Moreover, we observed an inverse relationship between the levels of microRNAs and six potential target mRNAs (B3GAT3, HNRNPL, OASL, ODZ3, CNGB1, and PKD2). Our results indicate that alterations in the level of a small number of microRNAs in response to smoking may contribute to changes in mRNA expression in smokers. We conclude that large-scale analysis of spermatozoa RNAs can be used to help understand the mechanisms by which human spermatogenesis responds to toxic substances including those in tobacco smoke.
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- 2015
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7. Structurally flexible triethanolamine core PAMAM dendrimers are effective nanovectors for DNA transfection in vitro and in vivo to the mouse thymus.
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Liu X, Wu J, Yammine M, Zhou J, Posocco P, Viel S, Liu C, Ziarelli F, Fermeglia M, Pricl S, Victorero G, Nguyen C, Erbacher P, Behr JP, and Peng L
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- Animals, DNA genetics, Green Fluorescent Proteins genetics, HeLa Cells, Humans, Mice, Mice, Inbred C57BL, DNA administration & dosage, Dendrimers chemistry, Ethanolamines chemistry, Thymus Gland metabolism, Transfection
- Abstract
With the aim of developing dendrimer nanovectors with a precisely controlled architecture and flexible structure for DNA transfection, we designed PAMAM dendrimers bearing a triethanolamine (TEA) core, with branching units pointing away from the center to create void spaces, reduce steric congestion, and increase water accessibility for the benefit of DNA delivery. These dendrimers are shown to form stable nanoparticles with DNA, promote cell uptake mainly via macropinocytosis, and act as effective nanovectors for DNA transfection in vitro on epithelial and fibroblast cells and, most importantly, in vivo in the mouse thymus, an exceedingly challenging organ for immune gene therapy. Collectively, these results validate our rational design approach of structurally flexible dendrimers with a chemically defined structure as effective nanovectors for gene delivery, and demonstrate the potential of these dendrimers in intrathymus gene delivery for future applications in immune gene therapy.
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- 2011
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8. Platelets alter gene expression profile in human brain endothelial cells in an in vitro model of cerebral malaria.
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Barbier M, Faille D, Loriod B, Textoris J, Camus C, Puthier D, Flori L, Wassmer SC, Victorero G, Alessi MC, Fusaï T, Nguyen C, Grau GE, and Rihet P
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- Apoptosis genetics, Brain metabolism, Endothelial Cells metabolism, Erythrocytes parasitology, Humans, Inflammation genetics, Malaria, Cerebral genetics, Plasmodium falciparum, Platelet Adhesiveness, Tumor Necrosis Factor-alpha pharmacology, Blood Platelets immunology, Brain pathology, Cell Communication immunology, Endothelial Cells pathology, Gene Expression Profiling, Malaria, Cerebral pathology
- Abstract
Platelet adhesion to the brain microvasculature has been associated with cerebral malaria (CM) in humans, suggesting that platelets play a role in the pathogenesis of this syndrome. In vitro co-cultures have shown that platelets can act as a bridge between Plasmodium falciparum-infected red blood cells (pRBC) and human brain microvascular endothelial cells (HBEC) and potentiate HBEC apoptosis. Using cDNA microarray technology, we analyzed transcriptional changes of HBEC in response to platelets in the presence or the absence of tumor necrosis factor (TNF) and pRBC, which have been reported to alter gene expression in endothelial cells. Using a rigorous statistical approach with multiple test corrections, we showed a significant effect of platelets on gene expression in HBEC. We also detected a strong effect of TNF, whereas there was no transcriptional change induced specifically by pRBC. Nevertheless, a global ANOVA and a two-way ANOVA suggested that pRBC acted in interaction with platelets and TNF to alter gene expression in HBEC. The expression of selected genes was validated by RT-qPCR. The analysis of gene functional annotation indicated that platelets induce the expression of genes involved in inflammation and apoptosis, such as genes involved in chemokine-, TREM1-, cytokine-, IL10-, TGFβ-, death-receptor-, and apoptosis-signaling. Overall, our results support the hypothesis that platelets play a pathogenic role in CM.
- Published
- 2011
- Full Text
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9. Spatial (Tbata) expression in mature medullary thymic epithelial cells.
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Saade M, Irla M, Yammine M, Boulanger N, Victorero G, Vincentelli R, Penninger JM, Holländer GA, Chauvet S, and Nguyen C
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- Animals, Antigens, Surface genetics, Antigens, Surface metabolism, Embryo, Mammalian cytology, Embryo, Mammalian embryology, Embryo, Mammalian metabolism, Female, Immunohistochemistry, In Situ Hybridization, Male, Membrane Glycoproteins genetics, Membrane Glycoproteins metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Nuclear Proteins metabolism, RANK Ligand genetics, RANK Ligand metabolism, Receptor Activator of Nuclear Factor-kappa B genetics, Receptor Activator of Nuclear Factor-kappa B metabolism, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Thymus Gland embryology, Thymus Gland growth & development, Time Factors, Transcription Factors genetics, Transcription Factors metabolism, AIRE Protein, Epithelial Cells metabolism, Gene Expression Regulation, Developmental, Nuclear Proteins genetics, Thymus Gland metabolism
- Abstract
The Spatial gene is expressed in highly polarized cell types such as testis germ cells, brain neurons and thymic epithelial cells (TEC). Its expression was documented in testis and brain but poorly characterized in thymus. Here, we characterize for the first time Spatial-expressing TEC throughout ontogeny and adult mouse thymus. Spatial is expressed in thymic-fated domain by embryonic day E10.5 and persists in subcapsular, cortical, medullary epithelial cells and in MTS24(+) progenitor TEC. Using mouse strains in which thymocyte development is blocked at various stages, we show that Spatial expression is independent of thymocyte-derived signals during thymus organogenesis. Analyses on purified thymic cell subsets show that Spatial short isoforms are expressed in cortical TEC (cTEC) and mature medullary TEC (mTEC). Spatial long isoforms were detected in the same TEC population. Spatial presents a nuclear distribution specific to mature mTEC expressing UEA1 and Aire. Aire- and RANKL-deficient mice revealed that Spatial expression is drastically reduced in the thymus of these mutants. These findings reveal a critical function of Aire in regulating Spatial expression, which is compatible with promiscuous Spatial gene expression.
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- 2010
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10. Neuronal distribution of spatial in the developing cerebellum and hippocampus and its somatodendritic association with the kinesin motor KIF17.
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Irla M, Saade M, Fernandez C, Chasson L, Victorero G, Dahmane N, Chazal G, and Nguyen C
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- Animals, Cells, Cultured, Cerebellum cytology, Gene Expression Profiling, Hippocampus cytology, Mice, Mice, Inbred C57BL, Neurons cytology, Protein Binding, Protein Isoforms metabolism, Protein Transport, Purkinje Cells cytology, Purkinje Cells metabolism, Subcellular Fractions metabolism, Cerebellum embryology, Dendrites metabolism, Hippocampus embryology, Kinesins metabolism, Molecular Motor Proteins metabolism, Neurons metabolism, Nuclear Proteins metabolism
- Abstract
We identified the Spatial (Stromal Protein Associated with Thymii and Lymph-node) gene from an adult thymus mouse library of cDNA clones. By RT-PCR, we reported that Spatial was highly expressed in restricted areas of the central nervous system. Here, we characterize the precise cellular localization of Spatial during mouse brain development in the cerebellum, hippocampus and cortex. Five different transcript isoforms have been described for Spatial and among those, only Spatial-epsilon and -beta present a tightly controlled expression. In the cerebellum, Spatial expression is detected in the external precursor granular layer and persists as these cells migrate and differentiate to form the internal granular layer. It is also expressed in differentiating Purkinje cells with a specific somatodendritic distribution. Spatial expression in the hippocampus is spatially and temporally regulated: it is first expressed in the CA3 field, then in CA1 and later in the dentate gyrus. Interestingly, Spatial-beta expression tightly overlaps with the beginning of neuronal differentiation in both structures. Using cultured hippocampal neurons, we show that Spatial also exhibits a somatodendritic distribution and it is concentrated in some synaptic regions. Moreover, the vesicle-like cellular distribution of Spatial protein in dendrites is similar to that described for the kinesin motor protein KIF17. Immunofluorescence analyses show that Spatial colocalizes with KIF17 in dendrites of hippocampal neurons in primary culture. Additionally, coimmunoprecipitation experiments of endogenous proteins from hippocampus confirmed that Spatial and KIF17 physically interact. These findings suggest that Spatial may play a role in neuronal morphogenesis and synaptic plasticity through its interaction with the kinesin motor KIF17 in dendrites.
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- 2007
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11. Dynamic distribution of Spatial during mouse spermatogenesis and its interaction with the kinesin KIF17b.
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Saade M, Irla M, Govin J, Victorero G, Samson M, and Nguyen C
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- Animals, Immunohistochemistry, Male, Mice, Mice, Inbred C57BL, Nuclear Proteins genetics, Protein Isoforms, Seminiferous Tubules metabolism, Sperm Maturation, Kinesins metabolism, Molecular Motor Proteins metabolism, Nuclear Proteins metabolism, Spermatogenesis, Spermatozoa metabolism, Testis metabolism
- Abstract
The Spatial gene is expressed in highly polarized cell types, such as epithelial cells in the thymus, neurons in the brain and germ cells in the testis. In this study, we report the characterization and distribution of Spatial proteins during mouse spermatogenesis. Besides Spatial-epsilon and -delta, we show that the newly described short isoform Spatial-beta is expressed specifically in round spermatids. Using indirect immunofluorescence, we detected Spatial in the cytosol of the early round spermatid. By the end stages of round spermatids, Spatial is concentrated at the opposite face of the acrosome near the nascent flagellum and in the manchette during the elongation process. Finally in mature sperm, Spatial persists in the principal piece of the tail. Moreover, we found that Spatial colocalizes with KIF17b, a testis-specific isoform of the brain kinesin-2 motor KIF17. This colocalization is restricted to the manchette and the principal piece of the sperm tail. Further, coimmunoprecipitation experiments of native proteins from testis lysates confirmed Spatial-KIF17b association through the long Spatial-epsilon isoform. Together, these findings imply a function of Spatial in spermatid differentiation as a new cargo of kinesin KIF17b, in a microtubule-dependent mechanism specific to the manchette and the principal piece of the sperm tail.
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- 2007
- Full Text
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12. A general survey of thymocyte differentiation by transcriptional analysis of knockout mouse models.
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Puthier D, Joly F, Irla M, Saade M, Victorero G, Loriod B, and Nguyen C
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- Animals, Cell Differentiation genetics, Cell Differentiation immunology, Cell Line, Cell Line, Transformed, Cell Proliferation, DNA Helicases, Gene Expression Profiling methods, Gene Rearrangement, T-Lymphocyte, Genes, T-Cell Receptor alpha genetics, Leukemia P388, Mice, Mice, Inbred C57BL, Multigene Family immunology, Nuclear Proteins biosynthesis, Nuclear Proteins genetics, Oligonucleotide Array Sequence Analysis methods, Proto-Oncogene Proteins deficiency, Proto-Oncogene Proteins genetics, Receptor, Notch1, Receptors, Cell Surface biosynthesis, Receptors, Cell Surface genetics, Receptors, Interleukin-2 biosynthesis, Stromal Cells immunology, Stromal Cells metabolism, T-Lymphocyte Subsets metabolism, Thymus Gland metabolism, Transcription Factor RelB, Transcription Factors biosynthesis, Transcription Factors deficiency, Transcription Factors physiology, Up-Regulation genetics, Up-Regulation immunology, Mice, Knockout genetics, Mice, Knockout immunology, Models, Animal, T-Lymphocyte Subsets cytology, T-Lymphocyte Subsets immunology, Thymus Gland cytology, Thymus Gland immunology, Transcription Factors genetics
- Abstract
The thymus is the primary site of T cell lymphopoiesis. To undergo proper differentiation, developing T cells follow a well-ordered genetic program that strictly depends on the heterogeneous and highly specialized thymic microenvironment. In this study, we used microarray technology to extensively describe transcriptional events regulating alphabeta T cell fate. To get an integrated view of these processes, both whole thymi from genetically engineered mice together with purified thymocytes were analyzed. Using mice exhibiting various transcriptional perturbations and developmental blockades, we performed a transcriptional microdissection of the organ. Multiple signatures covering both cortical and medullary stroma as well as various thymocyte maturation intermediates were clearly defined. Beyond the definition of histological and functional signatures (proliferation, rearrangement), we provide the first evidence that such an approach may also highlight the complex cross-talk events that occur between maturing T cells and stroma. Our data constitute a useful integrated resource describing the main gene networks set up during thymocyte development and a first step toward a more systematic transcriptional analysis of genetically modified mice.
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- 2004
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13. Genomic organization and the tissue distribution of alternatively spliced isoforms of the mouse Spatial gene.
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Irla M, Puthier D, Granjeaud S, Saade M, Victorero G, Mattei MG, and Nguyen C
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- Amino Acid Sequence, Animals, Cattle, Chromosome Mapping, Cosmids, Exons genetics, Humans, In Situ Hybridization, Fluorescence, Male, Mammals genetics, Mammals metabolism, Mice, Molecular Sequence Data, Nuclear Proteins chemistry, Nuclear Proteins metabolism, Organ Specificity, Protein Isoforms chemistry, Protein Isoforms genetics, Protein Isoforms metabolism, Protein Structure, Secondary, RNA Splice Sites, Rats, Reverse Transcriptase Polymerase Chain Reaction, Sequence Alignment, Sequence Homology, Amino Acid, Species Specificity, Sus scrofa, Testis metabolism, Thymus Gland metabolism, Alternative Splicing, Nuclear Proteins genetics
- Abstract
Background: The stromal component of the thymic microenvironment is critical for T lymphocyte generation. Thymocyte differentiation involves a cascade of coordinated stromal genes controlling thymocyte survival, lineage commitment and selection. The "Stromal Protein Associated with Thymii And Lymph-node" (Spatial) gene encodes a putative transcription factor which may be involved in T-cell development. In the testis, the Spatial gene is also expressed by round spermatids during spermatogenesis., Results: The Spatial gene maps to the B3-B4 region of murine chromosome 10 corresponding to the human syntenic region 10q22.1. The mouse Spatial genomic DNA is organised into 10 exons and is alternatively spliced to generate two short isoforms (Spatial-alpha and -gamma) and two other long isoforms (Spatial-delta and -epsilon) comprising 5 additional exons on the 3' site. Here, we report the cloning of a new short isoform, Spatial-beta, which differs from other isoforms by an additional alternative exon of 69 bases. This new exon encodes an interesting proline-rich signature that could confer to the 34 kDa Spatial-beta protein a particular function. By quantitative TaqMan RT-PCR, we have shown that the short isoforms are highly expressed in the thymus while the long isoforms are highly expressed in the testis. We further examined the inter-species conservation of Spatial between several mammals and identified that the protein which is rich in proline and positive amino acids, is highly conserved., Conclusions: The Spatial gene generates at least five alternative spliced variants: three short isoforms (Spatial-alpha, -beta and -gamma) highly expressed in the thymus and two long isoforms (Spatial-delta and -epsilon) highly expressed in the testis. These alternative spliced variants could have a tissue specific function.
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- 2004
- Full Text
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14. Large scale gene expression analysis of CBA/J mouse strain fetal thymus using cDNA-array hybridizations.
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Espanhol AR, Cardoso RS, Junta CM, Victorero G, Loriod B, Nguyen C, and Passos GA
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- Animals, Female, Gene Expression Profiling, Male, Mice, Mice, Inbred CBA, Thymus Gland embryology, Gene Expression Regulation, Developmental, Oligonucleotide Array Sequence Analysis methods, Thymus Gland metabolism
- Abstract
The CBA/J inbred mouse strain constitutes an interesting in vivo model-system for studies on molecular genetics of thymus ontogeny. Using RT-PCR method we have found previously that several immune system related genes as interleukins and MHC are differentially expressed. During this period the onset of T-cell receptor beta rearrangements also occur. To know which other genes are modulated during the ontogeny of the thymus, the mRNA expression levels of fetal thymus (15 and 16 days gestation) of CBA/J mouse strain were measured by hybridization with a set of four macroarrays containing a panel of 6,144 IMAGE cDNA clones from MTB thymus library. We found 145 differentially expressed sequences; 44 were up- and 101 down-regulated in the thymus at 15-16 days gestation. Among these sequences, only 20 are identified as genes whose functions are known and 125 are still unknown. Our data demonstrated that, despite intense research on maturation of the immune system focusing on the activity of several well-characterized genes, the large scale expression profile during thymus ontogeny is still an open matter. The use of cDNA-array technology is an affordable method to identify new genes that may play a role in this phenomenon.
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- 2004
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15. Gene expression profiling of colon cancer by DNA microarrays and correlation with histoclinical parameters.
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Bertucci F, Salas S, Eysteries S, Nasser V, Finetti P, Ginestier C, Charafe-Jauffret E, Loriod B, Bachelart L, Montfort J, Victorero G, Viret F, Ollendorff V, Fert V, Giovaninni M, Delpero JR, Nguyen C, Viens P, Monges G, Birnbaum D, and Houlgatte R
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- Colon metabolism, Colonic Neoplasms metabolism, Colonic Neoplasms physiopathology, Gene Expression Profiling, Humans, Immunohistochemistry, Lymph Nodes physiopathology, Neoplasm Metastasis genetics, Neoplasm Metastasis physiopathology, Oligonucleotide Array Sequence Analysis, Colonic Neoplasms genetics
- Abstract
Different diagnostic and prognostic groups of colorectal carcinoma (CRC) have been defined. However, accurate diagnosis and prediction of survival are sometimes difficult. Gene expression profiling might improve these classifications and bring new insights into underlying molecular mechanisms. We profiled 50 cancerous and noncancerous colon tissues using DNA microarrrays consisting of approximately 8000 spotted human cDNA. Global hierarchical clustering was to some extent able to distinguish clinically relevant subgroups, normal versus cancer tissues and metastatic versus nonmetastatic tumours. Supervised analyses improved these segregations by identifying sets of genes that discriminated between normal and tumour tissues, tumours associated or not with lymph node invasion or genetic instability, and tumours from the right or left colon. A similar approach identified a gene set that divided patients with significantly different 5-year survival (100% in one group and 40% in the other group; P=0.005). Discriminator genes were associated with various cellular processes. An immunohistochemical study on 382 tumour and normal samples deposited onto a tissue microarray subsequently validated the upregulation of NM23 in CRC and a downregulation in poor prognosis tumours. These results suggest that microarrays may provide means to improve the classification of CRC, provide new potential targets against carcinogenesis and new diagnostic and/or prognostic markers and therapeutic targets.
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- 2004
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16. Gene expression profiling during thymus ontogeny and its association with TCRVbeta8.1-Dbeta2.1 rearrangements of inbred mouse strains.
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Espanhol AR, Macedo C, Junta CM, Cardoso RS, Victorero G, Loriod B, Nguyen C, Jordan B, and Passos GA
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- Animals, Base Sequence, DNA Primers, Mice, Mice, Inbred Strains, Recombination, Genetic, Reverse Transcriptase Polymerase Chain Reaction, Species Specificity, Thymus Gland cytology, Gene Expression Profiling, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, Thymus Gland metabolism
- Abstract
The V(D)J recombination of TCRalpha and beta in early developing T-cells is a highly modulated phenomenon initiated and completed by recombinase complex (RAG-1 and RAG-2), and regulated by other gene products such as interleukins. To further evaluate the association of several other gene products with the evolution of TCRVbeta8.1 V(D)J rearrangements in vivo, the mRNA expression levels of seven interleukins, three cytokines, receptors TCRVbeta8.1 and IL-2Rbeta, MHC-I/MHC-II, RAG-1/ RAG-2 and retroviral superantigen MMTV(SW) were measured by RT-PCR during the fetal development of the thymus of three inbred mouse strains (Balb-c, C57B1/6 and CBA/J). Clustering using the Tree View software, was used to organize these genes based on similarity of expression patterns. Each strain displayed a different expression profile during thymus ontogeny. During the late developmental stage the most evident association was the kinetics of MMTV(SW) retrovirus, IL-2Rbeta and IL-7 overexpression with reduction of TCRVbeta8.1-D1beta2.1 rearrangement in the thymus of CBA/J mice. These data suggest a susceptibility of this strain to expression of MMTV(SW) upon reduction of the rearranged TCRVbeta8.1-Dbeta2.1 segment in developing thymocytes, with parallel IL-7 overexpression.
- Published
- 2003
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17. Spatial, a new nuclear factor tightly regulated during mouse spermatogenesis.
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Irla M, Puthier D, Le Goffic R, Victorero G, Freeman T, Naquet P, Samson M, and Nguyen C
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- Animals, Gene Expression Profiling, Male, Mice, Mice, Inbred C57BL, Nuclear Proteins biosynthesis, Spermatids metabolism, Spermatogenesis physiology, Testis metabolism, Nuclear Proteins genetics, Spermatogenesis genetics
- Abstract
In order to clarify general mechanisms of T cell development, we used array technology to identify genes differentially expressed between wild type and mutant mice thymuses. This quantitative differential screening leads to the isolation of Spatial, a putative transcription factor, expressed at high level in thymic cortical stromal cells. We report here, by RT-PCR on 48 distinct tissues that Spatial is also highly expressed in testis. Interestingly, the testicular expression is developmentally regulated, since it only appears in adult mice around 7-8 weeks of age. Analysis of purified testicular cell types show that Spatial expression is restricted to haploid round spermatids during spermiogenesis and the expression sites were further localized by in situ hybridization to step 2-10 spermatids. Thus, this recently described nuclear factor constitutes a new marker of the round spermatid stage that may play a key role in the control of male germ cell development.
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- 2003
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18. The chemokine TECK is expressed by thymic and intestinal epithelial cells and attracts double- and single-positive thymocytes expressing the TECK receptor CCR9.
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Wurbel MA, Philippe JM, Nguyen C, Victorero G, Freeman T, Wooding P, Miazek A, Mattei MG, Malissen M, Jordan BR, Malissen B, Carrier A, and Naquet P
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- Animals, Chemokines, CC genetics, DNA, Complementary analysis, Epithelial Cells chemistry, Intestinal Mucosa immunology, Mice, Mice, Inbred C57BL, Receptors, CCR, Receptors, Chemokine genetics, Reverse Transcriptase Polymerase Chain Reaction, Chemokines, CC analysis, Intestinal Mucosa chemistry, Receptors, Chemokine analysis, T-Lymphocytes chemistry, Thymus Gland chemistry
- Abstract
Chemokines are key regulators of migration in lymphoid tissues. In the thymus, maturing thymocytes move from the outer capsule to the inner medulla and thereby interact with different types of stromal cells that control their maturation and selection. In the process of searching for molecules specifically expressed at different stages of mouse thymic differentiation, we have characterized the cDNA coding for the thymus-expressed chemokine (TECK) and its receptor CCR9. The TECK receptor gene was isolated and shown to be localized on the mouse chromosome 9F1-F4. Thymic dendritic cells have been initially thought to be a prevalent source of TECK. In contrast, our results indicate that thymic epithelial cells constitute the predominant source of TECK. Consistent with the latter distribution, the TECK receptor is highly expressed by double-positive thymocytes, and TECK can chemoattract both double-positive and single-positive thymocytes. The TECK transcript is also abundantly expressed in the epithelial cells lining the small intestine. In conclusion, the interplay of TECK and its receptor CCR9 is likely to have a significant role in the recruitment of developing thymocytes to discrete compartments of the thymus.
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- 2000
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19. Modulation of mRNA levels in the presence of thymocytes and genome mapping for a set of genes expressed in mouse thymic epithelial cells.
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Rocha D, Carrier A, Naspetti M, Victorero G, Anderson E, Botcherby M, Guénet JL, Nguyen C, Naquet P, and Jordan BR
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- Animals, Coculture Techniques, Epithelial Cells, Epithelium physiology, Genome, Mice, RNA, Messenger analysis, T-Lymphocytes cytology, Thymus Gland cytology, Chromosome Mapping, Gene Expression Regulation, RNA, Messenger genetics, T-Lymphocytes physiology, Thymus Gland physiology
- Abstract
Modulation of gene expression in mouse thymic epithelium upon culture in the presence of thymocytes (coculture) was studied by comparison of hybridization signatures on a set of nearly 5000 mouse thymus cDNA clones. Forty-nine differentially expressed clones (usually down-regulated in coculture) were characterized by tag sequencing. Many of them corresponded to entities that had not been described previously in the mouse, and were further characterized by genome mapping. This set of genes appears to be involved in growth regulation and differentiation within the thymus.
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- 1997
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20. Multiplex messenger assay: simultaneous, quantitative measurement of expression of many genes in the context of T cell activation.
- Author
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Bernard K, Auphan N, Granjeaud S, Victorero G, Schmitt-Verhulst AM, Jordan BR, and Nguyen C
- Subjects
- Animals, Arabidopsis genetics, Base Sequence, Blotting, Northern, Cell Line, Cytochrome c Group genetics, DNA Probes, Epithelium metabolism, Mice, Molecular Sequence Data, Nucleic Acid Hybridization, Oligodeoxyribonucleotides, RNA, Messenger metabolism, Reproducibility of Results, Sensitivity and Specificity, T-Lymphocytes, Cytotoxic immunology, Gene Expression, Genetic Techniques, Lymphocyte Activation genetics, T-Lymphocytes immunology
- Abstract
The hybridization signature approach, using colony filters and labeled complex probes, can provide high throughput measurement of gene activity. We describe here the implementation of this method to follow the expression levels of 47 genes in resting and activated T cells, as well as in epithelial cells. Using 4-fold spotting of colonies, imaging plate detection and various correction and normalization procedures, the technique is sensitive enough to quantify expression levels for sequences present at 0.005% abundance in the probe. Comparison with Northern blotting shows good consistency between the two methods. Upon activation of a T cell clone by an anti-CD3 antibody variations ranging from 2- to 20-fold are measured, some of which had not been reported previously. This 'multiplex messenger assay' method, performed using available commercial apparatus, can be used in many cases where simultaneous assessment of mRNA levels for many genes is of interest.
- Published
- 1996
- Full Text
- View/download PDF
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