Project description:The cytokine transforming growth factor-B (TGF-B) regulates development and homeostasis of several tissue-resident macrophage populations, including microglia. TGF-B is not critical for microglia survival, but is required for the maintenance of the microglia-specific homeostatic gene signature. Under defined host conditions circulating monocytes can compete for the microglial niche and give rise to long-lived monocyte-derived macrophages residing in the central nervous system (CNS). Whether monocytes require TGF-B for colonization of the microglial niche and maintenance of CNS integrity is unknown. We found that abrogation of TGF-B signaling in CX3CR1+ monocyte-derived macrophages led to rapid onset of a progressive and fatal demyelinating motor disease characterized by myelin-laden giant macrophages throughout the spinal cord. The devastating motor disease that developed in TGF-BR2-deficient chimeras indicated that in the absence of TGF-B signaling the CNS environment licenses monocyte-derived macrophages for tissue damage. We therefore addressed how the gene expression signature of CNS macrophages was controlled by TGF-B signaling. We thus sorted TGF-BR2-deficient monocyte-derived macrophages from animals with ongoing motor disease and from their wildtype littermate counterparts. For comparison we sorted wild-type and TGF-BR2-deficient microglia and performed RNA sequencing for all four groups. Tgfbr2-deficient macrophages were characterized by high expression of genes encoding proteins involved in antigen presentation, inflammation and phagocytosis. TGF-B is thus crucial for the functional integration of monocytes into the CNS microenvironment.
Project description:Microglia contribute to maintaining brain homeostasis by interacting with neurons and macroglial cells through different signaling molecules. Here, we investigate the transcriptional profile of microglia lacking TGFbeta signaling given by inactivation of the Tgfbr2 gene, at three different stages of development. These microglia show a signature consistent with increased activation and impaired maturation, representing a state commonly associated with neurological pathologies.
Project description:Gene expression of hepatocyt-specific knockout of Pten and of Pten and Tgfbr2 in mice as a model for human cholangiocarcinoma was determined Affymetrix Mouse 1.0ST chips were used to measure gene expression Gene expression of the following mouse livers were characterized A. WT (n=3). B. Pten-/- (n=4). C. Pten-/- Tgfbr2-/- (n=4).
Project description:TGFBR2 was deleted in ovarian cancer TIL via CRISPR/Cas9 gene editing. Response of unmodified and TGFBR2 knockout TIL to TGF-B stimulation was evaluated via RNA sequencing.
Project description:Transforming growth factor beta receptor 2 (Tgfbr2) was predicted as a causal gene for abdominal using a novel statistical method named LCMS (Schadt et al., 2005, Nature Genetics). In order to validate this prediction, we profiled the liver tissues of Tgfbr2 heterozygous knockout mice (Tgfbr2+/-) and their littermate wild-type (wt) controls to examine the gene expression signature as well as pathways/networks resulting from the single gene perturbation. 6 Tgfbr2+/- mice and 4 wt controls were profiled. Reference pool included RNA extracted from the liver of 6 wt control mice. Dye-swap was involved in the profiling.
Project description:Microglia isolated from glioma patients gain anti-tumor activities upon poly (I:C) stimulation. Expression profiles of human tumor-infiltrating microglia/macrophages before (untreated) and after treatment with poly (I:C) for 48h (induced). Tumor-infiltrating microglia/macrophages were isolated from freshly excised brain tumors
Project description:Transforming growth factor beta receptor 2 (Tgfbr2) was predicted as a causal gene for abdominal using a novel statistical method named LCMS (Schadt et al., 2005, Nature Genetics). In order to validate this prediction, we profiled the liver tissues of Tgfbr2 heterozygous knockout mice (Tgfbr2+/-) and their littermate wild-type (wt) controls to examine the gene expression signature as well as pathways/networks resulting from the single gene perturbation.
Project description:Gene expression of hepatocyt-specific knockout of Pten and of Pten and Tgfbr2 in mice as a model for human cholangiocarcinoma was determined Affymetrix Mouse 1.0ST chips were used to measure gene expression