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:Brain metastasis (BrM) represents a challenging clinical issue. The most common treatment options are surgery and irradiation. Little is known about the complex cellular and molecular microenvironment of BrM, thus lacking molecular targets to combat this dismal disease. It is known that macrophages from the periphery (monocyte-derived macrophages, MDM) and microglia, the brain-resident macrophages, comprise the most abundant stromal cell types in BrM. However, it is not known if both cell types represent a homogeneous cell population with redundant functions or if there are differences due to their ontologic origin. Besides breast cancer and melanoma, the highest incidence of BrM can be found in lung cancer. To gain deeper insight into the myeloid immune landscape and the heterogeneity of BrM-associated immune cells, we here provide single cell RNA Seq data of microglia and MDMs which were associated with a lung cancer (LuCa) BrM, as well as with an irradiated LuCa BrM. Cells were FACS purified into 384 well plates, snap frozen on dry ice and single cell RNA-Seq performed. Together, our data hint towards cell type-specific heterogeneity both, before and upon application of irradiation.
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:Vascular smooth muscle cells (VSMC) are important for contraction, blood flow distribution and regulation of blood vessel diameter, but to what extent they contribute to the integrity of blood vessels and blood-brain barrier function is less well understood. In this report, we explored the impact of the progressive loss of VSMC in the Notch3-/- mouse on blood vessel integrity in the central nervous system To explore the molecular consequences of the VSMC phenotype in Notch3-/- mice, we performed genome-wide transcriptional profiling of the brain vasculature in mutants and littermate controls using Affymetrix Mouse Genome 430 2.0 Array. Three Notch3 knockout and three littermate control mice at age of 2 months were used to profile the transcriptomes. Total RNA was extracted from cerebral and cerebellar microvascular fragments and hyrbridized separately on the Mouse Genome 430 2.0 Array according to standard procedures.
Project description:Molecular mechanisms underlying the differentiation of brain mural cells from neural crest are poorly understood. We found that activation of Notch3 signaling in human pluripotent stem cell-derived neural crest (using lentiviral overexpression of the human Notch3 intracellular domain, N3ICD) was sufficient to direct the differentiation of mural cells. We used Notch3 ChIP-sequencing to identify cis-regulatory elements directly bound by the Notch3 transcriptional activation complex in this system.