Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset syndrome characterized by progressive degeneration of specific muscles. OPMD is caused by short GCN repeat expansions within the gene encoding the nuclear poly(A)-binding protein 1 (PABPN1) that extend an N-terminal polyalanine tract in the protein. Mutant PABPN1 aggregates as nuclear inclusions in OMPD patient muscles. We have used the transgenic mouse A17.1 OPMD model that recapitulates the features of the human disorder: progressive muscle weakness, atrophy and formation of PABPN1 nuclear inclusions. Wild-type human PABPN1 contains a stretch of 10 alanines following the initial methionine, which is expanded to 1118 alanines in OPMD patients. Transgenic A17.1 mouse overexpress an 17 alanine expanded PABPN1 under the control of the HSA promoter. To evaluate a gene therapy approach based on AAV delivery of a suppress and replace strategy in OPMD we performed a transcriptomic analysis in treated muscles 18 weeks after injection. Using microarrays, tibialis anterior gene expression was compared between control muscles (FvB), OPMD muscles (A17), AAV-shRNA3x treated muscles (A17 shRNA3X), AAVoptPABPN1 treated muscles (A17 optPABPN1), and AAV-shRNA3x+AAV-optPABPN1 treated muscles (A17 dual).
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Sex
View SamplesSatellite cells are the primary source of stem cells for skeletal muscle growth and regeneration. Since adult stem cell maintenance involves a fine balance between intrinsic and extrinsic mechanisms, we performed genome-wide chronological expression profiling to identify the transcriptomic changes involved in acquisition of muscle stem cell characteristics.
Gene Expression Profiling of Muscle Stem Cells Identifies Novel Regulators of Postnatal Myogenesis.
Age, Specimen part
View SamplesSatellite cells are the primary source of stem cells for skeletal muscle growth and regeneration. Since adult stem cell maintenance involves a fine balance between intrinsic and extrinsic mechanisms, we performed genome-wide chronological expression profiling to identify the transcriptomic changes involved during early postnatal growth till acquisition of satellite cell quiescence.
Pericytes in the myovascular niche promote post-natal myofiber growth and satellite cell quiescence.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Molecular subtypes of metastatic colorectal cancer are associated with patient response to irinotecan-based therapies.
Sex, Age
View SamplesTranscriptomic response of tumoral and normal brain tissue, treated with the MRT irradiation or the BB irradiation, after 6 h, 48 h, 8 days, 15 days, using Affymetrix GeneChip Rat 230_ 2.
No associated publication
Specimen part, Treatment, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan.
Sex, Age, Specimen part, Subject
View SamplesWithout treatment, HIV-1 infection is characterized in the majority of individuals by a detectable HIV replication and a rapid decline in CD4+ T lymphocytes leading to AIDS. However, a minority of patients, called HIV Controllers (HIC), maintains spontaneous control of HIV replication and for a large part, normal CD4+ T cell counts. The mechanisms leading to this spontaneous virus control are not fully known. We used gene expression and functional cellular analyses to compare EC and chronically HIV-1 infected individuals with controlled virus replication under combined antiretroviral therapy (cART). In the blood, EC individuals are characterized by a low inflammation, a down modulation of NK inhibitory cell signaling and an up regulation of T-cell activation gene expression profiles. Interestingly, in contrast to cART individuals, this balance persists following in vitro stimulation of cells from HIC with HIV antigens. This favourable genetic profile in HIC was also consistent with functional analyses showing a bias towards a Th1 and cytotoxic T cell profile and a lower production of inflammatory cytokines. Finally, taking advantage of the characterization of HIC based upon their in vitro CD8+ T lymphocyte capacity of killing HIV-infected cells, we show that unsupervised genetic analysis of differentially expressed genes fits clearly with this cytotoxic activity allowing the characterization of a specific signature of HIC individuals. Globally, these results reveal significant features of HIC making the bridge between cellular function and gene signatures and the regulation of inflammation and killing capacity of HIV-specific CD8+T cells. Moreover, these genetic profiles are consistent through analyses performed from whole blood to PBMC and at the T-cell population levels. Likely, these data help to define the goals of immunotherapeutic approaches in the perspective of HIV-1 functional cure. These strategies would need to induce both strong HIV-1-specific immune responses whereas minimizing inflammation.
No associated publication
Specimen part, Time
View SamplesWithout treatment, HIV-1 infection is characterized in the majority of individuals by a detectable HIV replication and a rapid decline in CD4+ T lymphocytes leading to AIDS. However, a minority of patients, called HIV Controllers (HIC), maintains spontaneous control of HIV replication and for a large part, normal CD4+ T cell counts. The mechanisms leading to this spontaneous virus control are not fully known. We used gene expression and functional cellular analyses to compare EC and chronically HIV-1 infected individuals with controlled virus replication under combined antiretroviral therapy (cART). In the blood, EC individuals are characterized by a low inflammation, a down modulation of NK inhibitory cell signaling and an up regulation of T-cell activation gene expression profiles. Interestingly, in contrast to cART individuals, this balance persists following in vitro stimulation of cells from HIC with HIV antigens. This favourable genetic profile in HIC was also consistent with functional analyses showing a bias towards a Th1 and cytotoxic T cell profile and a lower production of inflammatory cytokines. Finally, taking advantage of the characterization of HIC based upon their in vitro CD8+ T lymphocyte capacity of killing HIV-infected cells, we show that unsupervised genetic analysis of differentially expressed genes fits clearly with this cytotoxic activity allowing the characterization of a specific signature of HIC individuals. Globally, these results reveal significant features of HIC making the bridge between cellular function and gene signatures and the regulation of inflammation and killing capacity of HIV-specific CD8+T cells. Moreover, these genetic profiles are consistent through analyses performed from whole blood to PBMC and at the T-cell population levels. Likely, these data help to define the goals of immunotherapeutic approaches in the perspective of HIV-1 functional cure. These strategies would need to induce both strong HIV-1-specific immune responses whereas minimizing inflammation.
No associated publication
Specimen part
View SamplesWe report that previously described molecular subtypes of colorectal cancer are associated with the response to therapy in patients with metastatic disease. We also identified a patient population with high FOLFIRI sensitivity, as indicated by their 2.7-fold longer overall survival when treated with FOLFIRI, as first-line regimen, instead of FOLFOX. Our results demonstrate the interest of molecular classifications to develop tailored therapies for patients with metastatic colorectal cancer.
Molecular subtypes of metastatic colorectal cancer are associated with patient response to irinotecan-based therapies.
Sex, Age
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