Comparison between ex vivo immature, mature and stimulated T cells and in vitro generated counterparts. The T cells generated in vitro were cultured on OP9-DL1 stroma supplied with growth factors.
In vitro generation of mature, naive antigen-specific CD8(+) T cells with a single T-cell receptor by agonist selection.
Specimen part
View SamplesWe profiled RNA expression in human iPSC-derived ventricular and atrial cardiomyocytes Overall design: 4 biological replicates of human iPSC-derived ventricular cardiomyocytes and 4 biological replicates of iPSC-derived atrial cardiomyocytes (from 3 individual iPSC lines)
Deep phenotyping of human induced pluripotent stem cell-derived atrial and ventricular cardiomyocytes.
Specimen part, Cell line, Subject
View SamplesIn addition to helper and regulatory potential, CD4+T cells also acquire cytotoxic activity marked by granzyme B (GzmB) expression and the ability to promote rejection of established tumors. Here we examined the molecular and cellular mechanisms underpinning the differentiation of cytotoxic CD4+T cells following immunotherapy. CD4 transfer into lymphodepleted animals or regulatory T cell (Treg)depletion promoted GzmB expression by tumor-infiltrating CD4+which was prevented by IL-2 neutralization. Transcriptional analysis revealed a polyfunctional helper and cytotoxic phenotype characterized bythe expression of the transcription factors T-bet and Blimp-1. Whilst T-bet ablation restrictedIFN-gproduction, lossof Blimp-1preventedGzmB expressionin response to IL-2, suggesting these are two independent programs required forpolyfunctionality of tumor-reactive CD4+T cells. The data underscores the role of Treg, IL-2 and Blimp-1 controlling the differentiation of cytotoxic T cells and offers a pathway to enhancement of anti-tumor activity through their manipulation.
Regulatory T Cells Restrain Interleukin-2- and Blimp-1-Dependent Acquisition of Cytotoxic Function by CD4<sup>+</sup> T Cells.
Specimen part
View SamplesThe perception that soy food products and dietary supplements will have beneficial effects on heart health has led to a massive consumer market. However, we have previously noted that diet has a profound effect on disease progression in a genetic model of hypertrophic cardiomyopathy (HCM). In this model, a soy-based diet negatively impacts cardiac function in male mice.
Remodeling the cardiac transcriptional landscape with diet.
Sex, Specimen part
View SamplesWe Report the genome-wide RNA expression levels in control and schizophrenia hiPSC dervied NPC treated with neuronal media for 2 days. In total about 15,000 gene expression were detected in all samples, of which 1349 were dysregualted. Overall design: Examination, identification and comparision of mRNA expression profliles in control and schizophrenia npc
Common developmental genome deprogramming in schizophrenia - Role of Integrative Nuclear FGFR1 Signaling (INFS).
Specimen part, Subject
View SamplesUbiquitylation plays an important role in the control of Na+ homeostasis by the kidney. It is well established that the epithelial Na+ channel ENaC is regulated by the ubiquitin-protein ligase NEDD4-2, limiting ENaC cell surface expression and activity. Ubiquitylation can be reversed by the action of deubiquitylating enzymes (DUBs). One such DUB, USP2-45, was identified previously as an aldosterone-induced protein in the kidney, and is also a circadian output gene. In heterologous expression systems USP2-45 binds to ENaC, deubiquitylates it and enhances channel density and activity at the cell surface. Because the role of USP2-45 in renal Na+ transport had not been studied in vivo, we investigated here the effect of Usp2 gene inactivation in this process. We demonstrate first that the USP2-45 protein has a rhythmic expression with a peak at ZT12. Usp2-KO mice did not show any differences to wild-type littermates with respect to the diurnal control of Na+ or K+ urinary excretion and plasma levels neither on standard diet, nor after acute and chronic changes to low and high Na+ diets, respectively. Moreover, they had similar aldosterone levels either at low or high Na+ diet. Blood pressure measurements using telemetry did not reveal variations as compared to control mice. Usp2-KO did neither display alternations in ENaC or Na+,Cl--cotransporter (NCC) expression, nor were there any changes in regulatory protein levels, as evidenced by immunoblotting and transcriptome analysis. We conclude that USP2-45 is not crucial for the regulation of Na+ balance or maintenance of blood pressure in vivo.
Mice carrying ubiquitin-specific protease 2 (Usp2) gene inactivation maintain normal sodium balance and blood pressure.
No sample metadata fields
View SamplesPlasmacytoid dendritic cells (pDCs) rapidly produce type I interferon (IFN-I) in response to viruses and are essential for antiviral immune responses. Although related to classical dendritic cells (cDCs) in their development and expression profile, pDCs possess many distinct features. Unlike cDCs, pDCs develop in the bone marrow (BM) and emerge into peripheral lymphoid organs and tissues as fully differentiated cells. We now report that pDCs specifically express Runx2, a Runt family transcription factor that is essential for bone development. Runx2-deficient murine pDCs developed normally in the BM but were greatly reduced in the periphery. The defect was cell-intrinsic and was associated with the retention of mature Ly49Q+ pDCs in the BM. Runx2 was required for the expression of several pDC-enriched genes including chemokine receptors Ccr2 and Ccr5. Mature pDCs expressed high levels of Ccr5 at the surface, and Ccr5-deficient pDCs in a competitive setting were reduced in the periphery relative to the BM. Thus, Runx2 is required for the emergence of mature BM pDCs into the periphery, in a process that is partially dependent on Ccr5. These results establish Runx2 as a lineage-specific regulator of immune system development.
Transcription factor Runx2 controls the development and migration of plasmacytoid dendritic cells.
Specimen part
View SamplesSarcoidosis + Follow-up 6 month after
Functional genomics and prognosis in sarcoidosis--the critical role of antigen presentation.
No sample metadata fields
View SamplesSamples collected from human subjects in clinical trials possess a level of complexity, arising from multiple cell types, that can obfuscate the analysis of data derived from them. Blood, for example, contains many different cell types that are derived from a distinct lineage and carry out a different immunological purpose. Failure to identify, quantify, and incorporate sources of heterogeneity into an analysis can have widespread and detrimental effects on subsequent statistical studies.
Optimal deconvolution of transcriptional profiling data using quadratic programming with application to complex clinical blood samples.
Sex, Specimen part
View SamplesA LysM Receptor-like Kinase Mediates Chitin Perception and Fungal Resistance in Arabidopsis
A LysM receptor-like kinase plays a critical role in chitin signaling and fungal resistance in Arabidopsis.
No sample metadata fields
View Samples