Compartmentalization and persistence of dominant (regulatory) T cell clones indicates antigen skewing in juvenile idiopathic arthritis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA804209 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Autoimmune inflammation is characterized by tissue infiltration and expansion of antigen-specific T cells. Although this inflammation is often limited to specific target tissues, it remains yet to be explored whether distinct affected sites are infiltrated with the same, persistent T cell clones. Here, we performed CyTOF analysis and T cell receptor (TCR) sequencing to study immune cell composition and (hyper-)expansion of circulating and joint-derived Tregs and non-Tregs in juvenile idiopathic arthritis (JIA). We studied different joints affected at the same time, as well as over the course of relapsing-remitting disease. We found that the composition and functional characteristics of immune infiltrates are strikingly similar between joints within one patient, and observed a strong overlap between dominant T cell clones, especially Treg, of which some could also be detected in circulation and persisted over the course of relapsing-remitting disease. Moreover, these T cell clones were characterized by a high degree of sequence similarity, indicating the presence of TCR clusters responding to the same antigens. These data suggest that in localized autoimmune disease, there is autoantigen-driven expansion of both Teffector and Treg clones that are highly persistent and are (re)circulating. These dominant clones might represent interesting therapeutic targets.
| S-EPMC9995115 | biostudies-literature
Project description:We performed T cell receptor (TCR) sequencing to study immune cell composition and (hyper-)expansion of circulating and joint-derived Tregs and non-Tregs in Juvenile Idiopathic Arthritis (JIA, N=9). We studied different joints affected at the same time, as well as over the course of relapsing remitting disease.
2025-02-01 | GSE196301 | GEO
Project description:Background: Skewing root patterns provide key insights into root growth strategies and mechanism that produce root architectures Roots exhibit skewing and waving when grown on a tilted, impenetrable surface, and while the genetics guiding these morphologies have been examined, the underlying molecular mechanisms of skewing and waving remain unclear. In this study, transcriptome data were derived from two Arabidopsis ecotypes, WS and Col-0, under three tilted growth conditions in order to identify candidate genes involved in skewing. WS is a skewing ecotype. Col-0 is a non-skewing ecotype. Results: This work identifies a number of genes that are likely involved in skewing, using growth conditions that differentially affect skewing and waving. Comparing the gene expression profiles of WS and Col-0 in different tilted growth conditions identified 11 candidate genes as potentially involved in the control of skewing. These 11 genes are involved in several different cellular processes, including sugar transport, salt signaling, cell wall organization, and hormone signaling. Conclusions: Many of the 11 identified genes are involved in signaling and perception, rather than the physical restructuring of roots, leading to the conclusion that root skewing is enabled through diverse environmental signaling pathways. These findings revealed further insights into the molecular mechanisms behind root skewing. This work investigated the transcriptional differences between skewing and non-skewing roots. Comparisons within WS revealed gees that that responded to the angle of growth (Agp) during the process of skewing. These genes were cross referenced with transcripts differing between the WS and Col-0 genotypes to refine the list of genes that are most probably be involved in root skewing. More of the highly probable skew gene candidates (HPSGC) are associated with environmental sensing (e.g. salt, sugar, hormones, darkness) than with physical growth differences (e.g. cell wall remodeling, cell division, cell elongation). Thus, the root behavior of skewing appears to be primarily driven by pathways that respond to disparate signals from the root local environment. Future studies could investigate the HPSGC to find the specific pathways and molecular mechanisms contributing to root skewing.
2016-08-31 | GSE83242 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE35777: A molecular mechanism for compartmentalization and silencing of chromatin domains at the nuclear lamina [Tiling Array] GSE36048: A molecular mechanism for compartmentalization and silencing of chromatin domains at the nuclear lamina [ChIP-seq] Refer to individual Series
2012-02-24 | E-GEOD-36049 | biostudies-arrayexpress
Project description:It has recently been noted that empirical food webs are significantly compartmentalized; that is, subsets of species exist that interact more frequently among themselves than with other species in the community. Although the dynamic implications of compartmentalization have been debated for at least four decades, a general answer has remained elusive. Here, we unambiguously demonstrate that compartmentalization acts to increase the persistence of multitrophic food webs. We then identify the mechanisms behind this result. Compartments in food webs act directly to buffer the propagation of extinctions throughout the community and augment the long-term persistence of its constituent species. This contribution to persistence is greater the more complex the food web, which helps to reconcile the simultaneous complexity and stability of natural communities.
| S-EPMC3048152 | biostudies-literature
Project description:The aim of this study is to investigate whether there is selection for myeloid cells in our mouse models based on X chromosome choice. The mice are heterozygous at each allele for 129 & Bl6 mouse strains. We are investigating whether granulocyte RNA of female aged mice show a skewing towards one strain or the other at polymorphic loci of the X chromosome. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
2014-05-06 | E-ERAD-245 | biostudies-arrayexpress
Project description:RNA damage compartmentalization by DHX9 granules
| PRJNA902687 | ENA
Project description:Germ cells manifest a unique gene expression program and regain totipotency in the zygote. Here, we perform Hi-C analysis to examine 3D chromatin organization in male germ cells during spermatogenesis. We show that the highly compartmentalized 3D chromatin organization characteristic of interphase nuclei is attenuated in meiotic prophase. Meiotic prophase is predominated by short-range intrachromosomal interactions that represent a condensed form akin to that of mitotic chromosomes. However, unlike mitotic chromosomes, meiotic chromosomes display weak genomic compartmentalization, weak topologically associating domains, and localized point interactions in prophase. In postmeiotic round spermatids, genomic compartmentalization increases and gives rise to the strong compartmentalization seen in mature sperm. The X chromosome lacks domain organization during meiotic sex-chromosome inactivation. We propose that male meiosis occurs amid global reprogramming of 3D chromatin organization and that strengthening of chromatin compartmentalization takes place in spermiogenesis to prepare the next generation of life.
2019-02-18 | GSE119805 | GEO
Project description:How gene positioning to the nuclear periphery regulates transcription remains largely unclear. We have previously observed the differential compartmentalization of transcription factors and histone modifications at the nuclear periphery in mouse C2C12 myoblasts. Here, we have integrated high throughput DNA sequencing into the DNA adenine methyltransferase identification (DamID) assay, and have identified ~15, 000 sequencing-based Lamina-Associated Domains (sLADs) in mouse 3T3 fibroblasts and C2C12 myoblasts. These genomic regions range from a few kb to over 1 Mb and cover ~30% of the genome, and are spatially proximal to the nuclear lamina (NL). Active histone modifications such as H3K4me2, H3K9Ac, H3K36me3 and H3K79me2 are all localized away from the nuclear periphery microscopically, and distributed predominantly out of sLADs genome-wide. Therefore, the spatial compartmentalization of active histone modifications likely characterizes a major portion of chromatin at the nuclear periphery in mammalian cells. Genomic regions around transcription start sites of expressed sLAD genes display reduced associations with the NL and possess active histone modifications; in contrast, gene bodies of expressed sLAD genes possess very low levels of active histone modifications. Our genome-wide analyses of NL-associated chromatin have enabled functional and mechanistic dissections of gene positioning on transcription regulation. generate DamID maps of genome-NL interaction for mouse 3T3 fibroblasts and C2C12 myoblasts
2013-10-30 | E-GEOD-41583 | biostudies-arrayexpress
Project description:During mitosis, condensin activity is thought to disrupt interphase chromatin structures. Here, we utilize condensin-deficient mitotic chromosomes as a unique architectural platform to further investigate genome folding principles. Upon condensin loss, compartments progressively emerge in mitotic chromosomes. Euchromatin diverges into two different compartments A1 and A2, the former of which shows strong homotypic interactions while the latter exhibit reduced self-aggregation. Constitutive heterochromatin (B1) displays reduced level of compartmentalization and the normally inert facultative heterochromatin (B2) participates to compartmentalize the genome. Dynamically, A1 compartment is established remarkably fast with similarly efficient separation from B1 while reformation of B1 is delayed, implying that A1 self-attraction is the engine to compartmentalizalize the condensin-depleted mitotic chromosomes. Notified by the mitotic compartmentalization of B1 which lacks HP1 binding, we sought to explore the role of HP1 proteins in genome folding and demonstrat that HP1& are dispensible for chromatin structural restoration during cell divison. Our observations unveil delicate patterns and novel principles of genome compartmentalization that are otherwise hidden in interphase cells.
2023-11-22 | GSE228395 | GEO