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Human thymic putative CD8aa precursors exhibit a biased TCR repertoire in single cell AIRR-seq

ABSTRACT: Human thymic putative CD8aa precursors exhibit a biased TCR repertoire in single cell AIRR-seq

PROVIDER: PRJNA944993 | ENA |

REPOSITORIES: ENA

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Human thymic putative CD8aa precursors exhibit a biased TCR repertoire in single cell AIRR-seq

Project description:To explore the effect of the adaptive immune receptor repertoire on thymocyte developmental decisions, we performed single cell adaptive immune receptor repertoire sequencing (scAIRR-seq) of thymocytes from human young paediatric thymus and blood.

2023-08-18 | GSE227408 | GEO

Schwann cell precursors represent a neural crest-like hub state with biased multipotency

Project description:Schwann cell precursors represent a neural crest-like hub state with biased multipotency

| PRJNA830512 | ENA

KLRG1 and NKp46 expressing CD117+ human innate lymphoid cell precursors are biased to ILC2 and ILC3, respectively

Project description:Recently, circulating multi- and uni-potent human ILC precursors (ILCP) have been found in a lymphocyte population that expresses CD117 and CD127 but lacks CRTH2 and NKp44. However, these ILCPs have not been extensively characterized. We performed an unbiased Hierarchical Stochastic Neighbor Embedding (HSNE) analysis of the phenotype of peripheral blood CD117+ ILCPs which revealed the presence of three major subsets: the first expressed NKp46, the second expressed both NKp46 and CD56, while the third expressed KLRG1. Analysis of their differentiation potential on bulk and clonal levels, cytokine production and the transcriptome revealed that the NKp46+ ILCPs contain high frequencies of ILC3 precursors whereas a minority can differentiate into ILC1/NK-like cells. In contrast, KLRG1+ ILCPs are biased to the ILC2 lineage, but are highly plastic and epigenetically primed to differentiate into other ILC subsets depending on the activation signals they receive.

2019-06-05 | GSE124054 | GEO

Delineation of a conserved arrestin-biased signaling repertoire in vivo

Project description:Biased G protein-coupled receptor agonists engender a restricted repertoire of downstream events from their cognate receptors, permitting them to produce mixed agonist-antagonist effects in vivo. While this opens the possibility of novel therapeutics, it complicates rational drug design, since the in vivo response to a biased agonist cannot be reliably predicted from its in vitro efficacy. We have employed novel informatic approaches to characterize the in vivo transcriptomic signature of the arrestin pathway-selective parathyroid hormone analog [D-Trp12, Tyr34]-bPTH(7-34) in six different murine tissues after chronic drug exposure. We find that [D-Trp12, Tyr34]-bPTH(7-34) elicits a distinctive arrestin-signaling focused transcriptomic response that is more coherently regulated across tissues than that of the pluripotent agonist, hPTH(1-34). This arrestin-focused network is closely associated with transcriptional control of cell growth and development. Our demonstration of a conserved arrestin-dependent transcriptomic signature suggests a framework within which the in vivo outcomes of arrestin-biased signaling may be generalized.

2015-03-05 | GSE64485 | GEO

Seven chain adaptive immune receptor repertoire analysis in rheumatoid arthritis reveals novel features associated with disease and clinically relevant phenotypes

Project description:In rheumatoid arthritis (RA), the activation of T and B cell clones specific for self-antigens leads to the chronic inflammation of the synovium. Here, we perform an in-depth quantitative analysis of the seven chains that comprise the adaptive immune receptor repertoire (AIRR) in RA. In comparison to controls, we show that RA patients have multiple and strong differences in the BCR repertoire including reduced diversity as well as altered isotype, chain and segment frequencies. We demonstrate that therapeutic TNF inhibition partially restores this alteration but find a profound difference in the underlying biochemical reactivities between responders and non-responders. Combining the AIRR with HLA typing, we identify the specific TCR repertoire associated with disease risk variants. Integrating these features, we further develop a molecular classifier that shows the utility of the AIRR as a diagnostic tool. Simultaneous sequencing of the seven chains of the human AIRR reveals novel features associated with the disease and clinically relevant phenotypes, including response to therapy. These findings show the unique potential of AIRR to address precision medicine in immune-related diseases.

2024-02-23 | GSE256256 | GEO

Global expression profiling of peripheral Qa-1 class Ib-restricted CD8aa+TCRab+ regulatory T Cells reveals innate-like features: implications for immune regulatory repertoire

Project description:To better understand the function of CD8aa Tregs, we have recently characterized several CD8aa+TCRab+ T cell clones and lines that are physiologically primed and are involved in recovery and protection from EAE (REF). In this report, we present a comparison of global gene expression patterns in CD8aa Tregs versus OT-1 CD8aa+TCRab+ T cells. The results of microarray data analysis are confirmed by real-time PCR and flow cytometry for better accuracy and phenotype expression. Our study reveals a unique gene signature in the CD8aa Tregs, including enhanced expression of several inhibitory molecules associated with the maintenance of peripheral T cell homeostasis. The identification of differentially expressed molecules by CD8aa Tregs should facilitate future functional studies in this area.

2011-09-01 | GSE22985 | GEO

Global expression profiling of peripheral Qa-1 class Ib-restricted CD8aa+TCRab+ regulatory T Cells reveals innate-like features: implications for immune regulatory repertoire

2011-08-31 | E-GEOD-22985 | biostudies-arrayexpress

Schwann cell precursors represent a neural crest-like hub state with biased multipotency

Project description:Schwann cell precursors (SCPs) are nerve-associated progenitors that not only can generate myelinating and non-myelinating Schwann cells but also are multipotent like the neural crest cells from which they originate. SCPs are omnipresent along outgrowing peripheral nerves throughout the body of vertebrate embryos. By using single-cell transcriptomics to generate the atlas of the entire neural crest lineage, we show that early SCPs and late migratory crest have similar transcriptional profiles characterized by a multipotent “hub” state containing cells biased towards traditional neural crest fates. SCPs keep diverging from the neural crest after being primed towards terminal Schwann cell and other fates, with different subtypes residing in distinct anatomical locations. Functional experiments using CRISPR-Cas9 loss-of-function further show that knock-out of the hub gene Sox8 causes defects in neural crest-derived cells along peripheral nerves by facilitating differentiation of SCPs towards sympathoadrenal fates. Finally, specific tumour populations found in melanoma, neurofibroma and neuroblastoma map to different stages of SCP/Schwann cell development. Overall, SCPs resemble migrating neural crest cells that maintain multipotency and become transcriptionally primed toward distinct lineages.

2022-04-28 | GSE201257 | GEO

KLRG1 and NKp46 expressing CD117+ human innate lymphoid cell precursors are biased to ILC2 and ILC3, respectively

Project description:KLRG1 and NKp46 expressing CD117+ human innate lymphoid cell precursors are biased to ILC2 and ILC3, respectively

| PRJNA510626 | ENA

Mapping AT1R biased signaling using proximity-labeling and proteomics identifies diverse actions of biased agonists

Project description:Angiotensin II type 1 receptors (AT1Rs) are one of the most widely studied G protein-coupled receptors. To fully appreciate the diversity in cellular signaling profiles activated by AT1R transducer-biased ligands, we utilized peroxidase-catalyzed proximity labeling to capture proteins in close proximity to AT1Rs in response to six different ligands: Angiotensin II (full agonist), S1I8 (partial agonist), TRV055 and TRV056 (G protein-biased agonists), TRV026 and TRV027 (β-arrestin biased agonists) at 90s, 10min, and 60min after stimulation. We systematically analyzed the kinetics of AT1R trafficking and determined that distinct ligands lead AT1R to different cellular compartments for downstream signaling activation and receptor degradation/recycling. Distinct proximity labelling of proteins from a number of functional classes, including GTPases, adaptor proteins, and kinases were activated by different ligands suggesting unique signaling and physiological roles of the AT1R. Ligands within the same class, i.e. either G protein-biased or -arrestin-biased, shared high similarity in their labelling profiles. Comparison between ligand classes revealed distinct signaling activation such as greater labeling by G protein biased ligands on ESCRT-0 complex proteins that act as sorting machinery for ubiquitinated proteins. Our study provides a comprehensive analysis of AT1R receptor trafficking kinetics and signaling activation profiles induced by distinct classes of ligands.

2021-03-25 | PXD023814 | Pride

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