Reactive astrogliosis is characterized by a profound change in astrocyte phenotype in response to all CNS injuries and diseases. To better understand the reactive astrocyte state, we used Affymetrix GeneChip arrays to profile gene expression in populations of reactive astrocytes isolated at various time points after induction using two different mouse injury models, ischemic stroke and neuroinflammation.
Genomic analysis of reactive astrogliosis.
Sex, Specimen part, Treatment
View SamplesGliomas are the most devastating of primary adult malignant brain tumors. These tumors are highly infiltrative and can arise from cells with extensive self-renewal capability and chemoresistance, frequently termed glioma-propagating cells (GPCs). GPCs are thus the plausible culprits of tumor recurrence. Treatment strategies that eradicate GPCs will greatly improve disease outcome. Such findings support the use of GPCs as in vitro cellular systems for small molecule screening. However, the nuances in utilizing GPCs as a cellular screening platform are not trivial. These slow-growing cells are typically cultured as suspension, spheroid structures in serum-free condition supplemented with growth factors. Consequently, replenishment of growth factors throughout the screening period must occur to maintain cells in their undifferentiated state, as the more lineage-committed, differentiated cells are less tumorigenic. We will present a case study of a small molecule screen conducted with GPCs and explain how unique sphere activity assays were implemented to distinguish drug efficacies against the long-term, self-renewing fraction, as opposed to transient-amplifying progenitors, latter of which are detected in conventional viability assays. We identified Pololike kinase 1 as a regulator of GPC survival. Finally, we leveraged on public glioma databases to illustrate GPC contribution to disease progression and patient survival outcome.
Glioma-propagating cells as an in vitro screening platform: PLK1 as a case study.
Specimen part, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Zinc finger protein Zfp335 is required for the formation of the naïve T cell compartment.
Specimen part
View SamplesThis study provides the dectin-1 and NFAT responsive genes for 2h and 4h of curdlan treatment.
NFATc2 mediates epigenetic modification of dendritic cell cytokine and chemokine responses to dectin-1 stimulation.
Specimen part
View SamplesSteer mesenteric fat transcriptome.
Relationships between the genes expressed in the mesenteric adipose tissue of beef cattle and feed intake and gain.
Specimen part
View SamplesDendritic cells (DCs) are crucial for sensing pathogens and triggering immune response. GM-CSF myeloid dendritic cells (GM-DCs) secrete several cytokines including IL-2 upon activation by pathogen associated molecular pattern (PAMP) ligands. DC IL-2 has been shown to be important for innate and adaptive immune responses, however its importance in DC physiology has never been demonstrated. This is due to ambiguity in expression of the CD122 subunit of the IL-2 trimeric receptor complex crucial for signaling. We show here that autocrine IL-2 signaling is functional in GM-DCs in early time window of stimulation with PAMPs. IL-2 signaling selectively activates the JAK/STAT5 pathway by assembling holo-receptor complexs at the cell surface. Autocrine IL-2 signaling inhibits survival of PAMP matured GM-DCs which is crucial for maintaining immune tolerance and preventing autoimmunity. Our findings suggest immune regulation by a novel autocrine signaling pathway that can potentially be exploited in DC immunotherapy.
Dendritic cell derived IL-2 inhibits survival of terminally mature cells via an autocrine signaling pathway.
Specimen part
View SamplesThe generation of nave T lymphocytes is critical for immune function yet the mechanisms governing their maturation remain incompletely understood. We have identified a mouse mutant, bloto, that harbors a hypomorphic mutation in the zinc finger protein Zfp335. Mutant blt/blt mice exhibit a nave T cell deficiency due to an intrinsic developmental defect that begins to manifest in the thymus and continues into the periphery, affecting T cells that have recently undergone thymic egress. Zfp335 binds to promoter regions via a consensus motif, and its target genes are enriched in categories related to protein metabolism, mitochondrial function and transcriptional regulation. Restoring the expression of one target, Ankle2, partially rescues T cell maturation. Our findings identify Zfp335 as a transcription factor and essential regulator of late-stage intrathymic and post-thymic T cell maturation.
Zinc finger protein Zfp335 is required for the formation of the naïve T cell compartment.
Specimen part
View SamplesThe generation of nave T lymphocytes is critical for immune function yet the mechanisms governing their maturation remain incompletely understood. We have identified a mouse mutant, bloto, that harbors a hypomorphic mutation in the zinc finger protein Zfp335. Mutant blt/blt mice exhibit a nave T cell deficiency due to an intrinsic developmental defect that begins to manifest in the thymus and continues into the periphery, affecting T cells that have recently undergone thymic egress. Zfp335 binds to promoter regions via a consensus motif, and its target genes are enriched in categories related to protein metabolism, mitochondrial function and transcriptional regulation. Restoring the expression of one target, Ankle2, partially rescues T cell maturation. Our findings identify Zfp335 as a transcription factor and essential regulator of late-stage intrathymic and post-thymic T cell maturation.
Zinc finger protein Zfp335 is required for the formation of the naïve T cell compartment.
Specimen part
View SamplesTreatment of post-transplant patients with immunosuppressive drugs targeting the calcineurin-NFAT pathway, such as Cyclosporine A or Tacrolimus, are commonly associated with a higher incidence of opportunistic infections, such as Aspergillus fumigatus, which can lead to severe life-threating conditions. A component of the A. fumigatus cell wall, -glucan, is recognized by dendritic cells via the Dectin-1 receptor, triggering downstream signaling that leads to calcineurin-NFAT binding, NFAT translocation, and transcription of NFAT-regulated genes. Here, we address the question of whether calcineurin signaling in CD11c-expressing cells, such as DCs, has a specific role in the innate control of A. fumigatus. Impairment of calcineurin in CD11c-expressing cells (CD11ccrecnb1loxP) significantly increased susceptibility to systemic A. fumigatus infection and to intranasal infection in irradiated mice undergoing bone marrow transplant. Global expression profiling of bone marrow-derived DCs identified calcineurin-regulated processes in the immune response to infection, including expression of pentraxin-3, an important anti-fungal defense protein. These results suggest that calcineurin inhibition directly impairs important immunoprotective functions of myeloid cells, as shown by the higher susceptibility of CD11ccrecnbloxP mice in models of systemic and invasive pulmonary aspergillosis, including after allogeneic bone marrow transplantation. These findings are relevant to the clinical management of transplant patients with severe Aspergillus infections.
Impaired calcineurin signaling in myeloid cells results in downregulation of pentraxin-3 and increased susceptibility to aspergillosis.
Specimen part
View SamplesSteer small intestine transcriptome
Differential gene expression in the duodenum, jejunum and ileum among crossbred beef steers with divergent gain and feed intake phenotypes.
Specimen part
View Samples