Ontology highlight
ABSTRACT:
PROVIDER: PRJNA397547 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The presented data corresponds to the analysis of two discrete subsets of human CD8+ naive T cells, defined by positive and negative expression of the chemokine receptor CXCR3 (TNR3-, TNR3+). In this study we demonstrated that these subsets have different potential to generate fully-differentiated effector T cells following antigen-specific stimulation. The performed systematic immune repertoire analysis (T cell receptor beta chain (TRB)) of the sorted cell subsets revealed diverse physico-chemical properties of TRB CDR3 sequences suggesting enhanced TCR self-reactivity in human TNR3+ cells. In total, we analyzed 74 samples (from 11 patients, 3 replicates of each cell subset (excluding one missing replicate) and additionally for 3 patients CD8+ memory T cells in 3 replicates). We used the Human TCR Profiling Kit (MiLaboratory LLC) for sequencing libraries preparation and Illumina NextSeq 550 sequencing (150+150bp) followed by the demultiplexing procedure using MIGEC software (https://github.com/mikessh/migec).
2019-10-17 | E-MTAB-7638 | biostudies-arrayexpress
Project description:The potential protective or pathogenic role of the adaptive immune response to SARS-CoV-2 infection has been vigorously debated. While COVID-19 patients consistently generate a T cell response to SARS-CoV-2 antigens, evidence of significant immune dysregulation in these patients continues to accumulate. In this study, next generation sequencing of the T cell receptor Beta chain (TRB) repertoire was conducted in hospitalized COVID-19 patients to determine if immunogenetic differences of the TRB repertoire contribute to the severity of the disease course. Clustering of highly similar TRB CDR3 amino acid sequences across COVID-19 patients yielded 785 shared TRB sequences. The TRB sequences were then filtered for known associations with common diseases such as EBV and CMV. The remaining sequences were cross-referenced to a publicly accessible dataset that mapped COVID-19 specific TCRs to the SARS-CoV-2 genome. We identified 140 SARS-CoV-2 specific TRB sequences belonging to 119 clusters in our COVID-19 patients. Next, we investigated 92 SARS-CoV-2 specific clusters binding only one peptide target in relation to disease course. Distinct skewing of SARS-CoV-2 specific TRB sequences towards the nonstructural proteins (NSPs) of ORF1a/b of the SARS-CoV-2 genome was observed in clusters with critical disease course when compared to COVID-19 clusters with a severe disease course. These data imply that T-lymphocyte reactivity towards peptides from nonstructural proteins of SARS-CoV-2 may not constitute an effective adaptive immune response and thus may negatively affect disease severity.
2021-07-07 | GSE161810 | GEO
Project description:We show that an effective GvL is associated with a substantial drop of CD8+ TRB diversity and a concomitant expansion of dominant clones.
2020-11-16 | GSE161508 | GEO
Project description:We co-cultured T cells with Mo-DCs exposed to ConA for 24 h and used multiplex PCR and next-generation sequencing to detect the TCRα repertoire.The length of the amino acids of CDR3 in each group was 4–59 amino acids, and all presented a normal distribution. Moreover, the length of the amino acids of CDR3 was not different between ConA and control groups. The number of clonotypes and unique clonotypes in the ConA group was increased significantly compared with that in control groups. However, the difference of high-frequency CDR3 amino-acid clonotypes between ConA and control groups was not significant (cutoff = 0.2%). Our results for the V and J gene segments of TCR diversity showed a marked increase in the number of clonotypes in the ConA group. The Shannon–Wiener Diversity Index of ConA was lower than that in the control group, and the top-20 V and J gene segments of ConA showed a higher usage frequency than that in the control group, but the difference between ConA and the control group was not significant. Collectively, these data indicated that ConA could reduce CDR3 diversity and augment usage of high-frequency CDR3.
2022-05-15 | GSE163933 | GEO
Project description:In this study we used the d337T TRb transgenic mouse that has been created to reproduce the human genetic disease known as resistance to thyroid hormone (RTH) as a model to determine if the d337T TRb mutation would have an effect on PPARa activation. A single amino acid deletion (d337T) abrogates thyroid hormone (T3) binding and transforms the thyroid hormone receptor (TRb) into a constitutive repressor. The principle goal was to determine if T3 regulates myocardial energy metabolism through its nuclear receptors. We introduced a known PPARa activator (WY14, 643) into control and d337T TRb transgenic mice then examined cardiac gene expression using Affymetrix 430_2 expression arrays and RT-PCR. We compared the gene expression of PPARa, RXRb and TRa,b and three PPARa target genes among four studies groups [control, control with WY14, 643, d337T TRb, and d337T TRb with WY14, 643] consisting of seven mice per group. Microarray analysis revealed that these genes responded to the WY14, 643 treatments of control and d337T TRb mice. Analysis of the array and RT-PCR data indicates that mRNA expression levels of PPARa and mRXRb decrease after a six hour drug treatment in both control and d337T TRb mice (P<0.01) as did the array mRNA expression levels for TRa & b (P<0.025). Three target genes (AMPD3, PDK4 and UCP3) of PPARa were up regulated in control and down regulated in the d337T TRb transgenic mouse, indicating a direct action on these metabolic genes when the TRb becomes a repressor. In conclusion, PPARa activation by WY14, 643 has a positive effect on control mice and a negative effect on the TRb transgenic mice which supports our hypothesis that T3 regulates myocardial energy metabolism through its nuclear receptors. Experiment Overall Design: 7 control, 7 deletion strain individuals, 7 controls with a PPARalpha activator, 7 deletion strain individuals with a PPARalpha activator
2007-11-22 | E-GEOD-3067 | biostudies-arrayexpress
Project description:Transcriptional regulation in response to thyroid hormone (3,5,3´-triiodo-L-thyronine, T3) is a dynamic and cell-type specific process that maintains cellular homeostasis and identity in all tissues. However, our understanding of the mechanisms of thyroid hormone receptor (TR) actions at the molecular level are actively being refined. We used an integrated genomics approach to profile and characterize the cistrome of TRb, map changes in chromatin accessibility, and capture the transcriptomic changes in response to T3 in normal human thyroid cells. There are significant shifts in TRb genomic occupancy in response to T3, which are associated with differential chromatin accessibility, and differential recruitment of SWI/SNF chromatin remodelers. We further demonstrate selective recruitment of BAF and PBAF SWI/SNF complexes to TRb binding sites, revealing novel differential functions in regulating chromatin accessibility and gene expression. Our findings highlight three distinct modes of TRb interaction with chromatin and coordination of coregulator activity.
2022-04-04 | PXD030403 | Pride
Project description:Here, we describe a mouse model in which the primary B cell receptor (BCR) repertoire is generated solely through V(D)J recombination of a human VH1-2 heavy chain (HC) and, substantially, a human Vk1-33 light chain (LC). Thus, primary humanized BCR repertoire diversity in these mice derives from immensely diverse HC and LC antigen-contact complementarity-region-3 (CDR3) sequences generated de novo by non-templated junctional modifications during V(D)J recombination. We assayed the V usage and CDR3 diversity in this mouse model by HTGTS-repertoire sequencing. Immunizing this human VH1-2/Vk1-33-rearranging model with prototype SARS-CoV-2 spike protein immunogens elicited several VH1-2/Vk1-33-based nAbs. Of these, SP1-77 potently and broadly neutralized all SARS-CoV-2 variants through BA.5. Cryo-EM studies revealed that SP1-77 binds RBD away from the ACE2 receptor-binding-motif via a striking CDR3-dominated mode of recognition. Lattice-light-sheet-microscopy-based studies confirmed that SP1-77 did not block ACE2-mediated viral attachment or subsequent endocytosis, but rather blocked membrane fusion. The SP1-77 binding epitope and neutralization mechanism may offer additional strategies for designing vaccines that robustly neutralize emerging SARS-CoV-2 variants.
2022-07-28 | GSE197255 | GEO
Project description:In this study we used the d337T TRb transgenic mouse that has been created to reproduce the human genetic disease known as resistance to thyroid hormone (RTH) as a model to determine if the d337T TRb mutation would have an effect on PPARa activation. A single amino acid deletion (d337T) abrogates thyroid hormone (T3) binding and transforms the thyroid hormone receptor (TRb) into a constitutive repressor. The principle goal was to determine if T3 regulates myocardial energy metabolism through its nuclear receptors. We introduced a known PPARa activator (WY14, 643) into control and d337T TRb transgenic mice then examined cardiac gene expression using Affymetrix 430_2 expression arrays and RT-PCR. We compared the gene expression of PPARa, RXRb and TRa,b and three PPARa target genes among four studies groups [control, control with WY14, 643, d337T TRb, and d337T TRb with WY14, 643] consisting of seven mice per group. Microarray analysis revealed that these genes responded to the WY14, 643 treatments of control and d337T TRb mice. Analysis of the array and RT-PCR data indicates that mRNA expression levels of PPARa and mRXRb decrease after a six hour drug treatment in both control and d337T TRb mice (P<0.01) as did the array mRNA expression levels for TRa & b (P<0.025). Three target genes (AMPD3, PDK4 and UCP3) of PPARa were up regulated in control and down regulated in the d337T TRb transgenic mouse, indicating a direct action on these metabolic genes when the TRb becomes a repressor. In conclusion, PPARa activation by WY14, 643 has a positive effect on control mice and a negative effect on the TRb transgenic mice which supports our hypothesis that T3 regulates myocardial energy metabolism through its nuclear receptors. Keywords: treatment and deletion effects
2005-09-26 | GSE3067 | GEO
Project description:One antifungal agent, terbinafine(TRB), has specific activity against dermatophytes.A cDNA microarray was constructed from the expressed sequence tags (ESTs) of different developmental stages, and transcriptional profiles of the responses to TRB were determined. Some class-specific and mechanism-independent changes in gene expression were found. Keywords: original article The expression profiles of Trichophyton rubrum treated with TRB were compared to those of Trichophyton rubrum without drug. Each treatment has three replicates.
2010-06-26 | E-GEOD-6951 | biostudies-arrayexpress
Project description:The thyroid hormone receptor beta (TRβ), a key regulator of cellular growth and differentiation, is frequently dysregulated in cancers. Diminished expression of TRb is noted in thyroid, breast, and other solid tumors and is correlated with more aggressive disease. Restoration of TRb levels decreased tumor growth supporting the concept that TRb could function as a tumor suppressor. Yet, the TRb tumor suppression transcriptome is not well delineated and the impact of TRb is unknown in aggressive anaplastic thyroid cancer (ATC). Here, we establish that restoration of TRb expression in the human ATC cell line SW1736 (SW-TRβ) reduces the aggressive phenotype, decreases cancer stem-cell populations and induces cell death in a T3-dependent manner. Transcriptomic analysis of SW-TRβ cells via RNA-sequencing revealed distinctive expression patterns induced by ligand-bound TRβ and revealed novel molecular signaling pathways. Of note, liganded TRβ repressed multiple nodes in the PI3K/AKT pathway, induced expression of thyroid differentiation markers, and promoted pro-apoptotic pathways. Our results further revealed the JAK1-STAT1 pathway as a novel, T3-mediated, anti-tumorigenic pathway that can be activated in additional ATC lines. These findings elucidate a TRb-driven tumor suppression transcriptomic signature, highlight unexplored therapeutic options for ATC, and support TRb activation as a promising therapeutic option in cancers.
2020-05-13 | GSE150364 | GEO