This SuperSeries is composed of the SubSeries listed below.
Establishment of human iPSC-based models for the study and targeting of glioma initiating cells.
Specimen part, Cell line, Treatment
View SamplesGliomas can originate upon transformation of adult Neural Progenitor Cells (NPCs) to Tumor Initiating Cells (TICs). Studies on human Glioma TICs (GTICs) have focused on the use of primary tumors from which GTICs could be isolated. Therefore investigations on the driver events underlying NPC transformation and human glioma initiation remain limited to the use of human embryonic material. Here we report on the development of strategies for the modeling of human gliomagenesis based on the use of human induced Pluripotent Stem Cells (hiPSCs). Transformation of hiPSC-derived NPCs (iNPCs) by defined genetic alterations led to the establishment of tractable human GTIC models suitable for studying the early steps of gliomagenesis as well as for screening studies. Dysregulation of PI3K, MAPK and p53 signaling in iNPCs led to the acquisition of functional GTIC properties. In vivo transplantation led to the formation of highly aggressive, infiltrative and heterogeneous tumors upon limited dilutions and secondary transplantation, faithfully recapitulating gliomagenesis. Metabolic modulation by chemical approaches compromised GTIC viability. Pilot screening of 101 anti-cancer compounds identified 3 molecules specifically targeting transformed iNPCs and primary GTICs. Together, our results demonstrate the potential of hiPSCs for the functional testing of putative driver mutations underlying human tumorigenesis and pave new avenues for the development of personalized cancer therapeutics.
Establishment of human iPSC-based models for the study and targeting of glioma initiating cells.
Specimen part, Cell line, Treatment
View SamplesNAP - neuroprotective peptide demonstrates increase in neuronal survival when injected into the hippocampus of rats in the model of epilepsy
The microtubule interacting drug candidate NAP protects against kainic acid toxicity in a rat model of epilepsy.
No sample metadata fields
View SamplesSingle cell transcriptomic analysis of wildtype and AireKO thymic epithelial cells Overall design: Single cells were sorted by FACS for single cell RNAseq library preparation
Aire controls gene expression in the thymic epithelium with ordered stochasticity.
No sample metadata fields
View SamplesMicroarray profiles of splenic Tregs and Tconvs from Flicr WT and KO mice
<i>Flicr</i>, a long noncoding RNA, modulates Foxp3 expression and autoimmunity.
Sex, Age
View SamplesWe reported transcriptional characterization of Treg and Tconv cells from thymic, splenic, and visceral adipose tissue (VAT) of vTreg53 TCR transgenic mice and control littermates. We examined the effect of Foxp3 on splenic and VAT CD4+ T cell transcriptome. We profiled gene expression in a novel PPARg+ splenic Treg population. We uncovered that the characteristic phenotype of VAT Treg cells was acquired in two stages. Overall design: Gene expression profiles of thymic, splenic, VAT Treg, Tconv, and Foxp3-transduced Tconv cells from vTreg53 TCR transgenic and PPARg reporter mice.
TCR Transgenic Mice Reveal Stepwise, Multi-site Acquisition of the Distinctive Fat-Treg Phenotype.
Specimen part, Cell line, Subject
View SamplesRegulatory T cells (Tregs) are key brakes on the VAT inflammation that regulates local and systemic metabolic tenor. The cytokine, IL-33, expands and sustains the unique Treg population residing within VAT. Making use of single-cell RNA sequencing, we identified the major IL-33 producers in VAT to be particular mSC subtypes, related to but distinct from adipocyte progenitor cells. We further characterize these subsets by individually isolating them and performing bulk-RNA sequencing. We explored modulation of the VAT-mSC (VmSC) landscape with physiologic variables such as age and sex, as well as pathogenic states like obesity. We uncovered a VAT Treg:stromal-cell negative regulatory loop that keeps the potent effect of IL-33 under rein. Overall design: Gene expression profiles of VmSC subtypes from young male and female mice. 2-4 mice were pooled for each biological replicate and at least 2 biological replicates were obtained per VmSC subtype.
Distinct immunocyte-promoting and adipocyte-generating stromal components coordinate adipose tissue immune and metabolic tenors.
Specimen part, Cell line, Subject
View SamplesWe have determined that tenascin C (TNC) regulates the growth of human brain tumor initiating cells (BTICs). We have identified novel mechanisms by which TNC regulates BTIC growth. Analysis of the array data identified a number of genes that were altered with TNC treatment that could potentially regulate BTIC growth. The study provides the mechanistic basis for the regulation of BTIC growth with TNC.
Activation of NOTCH Signaling by Tenascin-C Promotes Growth of Human Brain Tumor-Initiating Cells.
Specimen part, Cell line, Treatment
View SamplesConditional ablation of Ezh2 in the neural crest lineage results in loss of the neural crest-derived mesenchymal derivatives. In this data sheet we determine gene expression analysis in Ezh2lox/lox and Wnt1Cre Ezh2lox/lox in E11.5 mouse BA1 cells.
Ezh2 is required for neural crest-derived cartilage and bone formation.
Specimen part
View SamplesOncogenic transformation by adenovirus small e1a depends on simultaneous interactions with the host lysine acetylases p300/CBP and the tumor suppressor RB. How these interactions influence cellular gene expression remains unclear. We find that e1a displaces RBs from E2F transcription factors and promotes p300 acetylation of RB1 K873/K874 to lock it into a repressing conformation that interacts with repressive chromatin-modifying enzymes. These repressing p300-e1a-RB1 complexes specifically interact with host genes that have unusually high p300 association within the gene body. The TGF?-, TNF-, and interleukin-signaling pathway components are enriched among such p300-targeted genes. The p300-e1a-RB1 complex condenses chromatin in a manner dependent on HDAC activity, p300 lysine acetylase activity, the p300 bromodomain, and RB K873/K874 and e1a K239 acetylation to repress host genes that would otherwise inhibit productive virus infection. Thus, adenovirus employs e1a to repress host genes that interfere with viral replication. Overall design: Examination of transcriptome by mRNA sequencing before and after infection by adenoviral e1a expressing vectors in growth arrested IMR90
Adenovirus small E1A employs the lysine acetylases p300/CBP and tumor suppressor Rb to repress select host genes and promote productive virus infection.
No sample metadata fields
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