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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 CD8αα precursors exhibit a biased TCR repertoire in single cell AIRR-seq.

Project description:Thymic T cell development comprises T cell receptor (TCR) recombination and assessment of TCR avidity towards self-peptide-MHC complexes presented by antigen-presenting cells. Self-reactivity may lead to negative selection, or to agonist selection and differentiation into unconventional lineages such as regulatory T cells and CD8[Formula: see text] T cells. 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 thymi and blood. Thymic PDCD1+ cells, a putative CD8[Formula: see text] T cell precursor population, exhibited several TCR features previously associated with thymic and peripheral ZNF683+ CD8[Formula: see text] T cells, including enrichment of large and positively charged complementarity-determining region 3 (CDR3) amino acids. Thus, the TCR repertoire may partially explain the decision between conventional vs. agonist selected thymocyte differentiation, an aspect of importance for the development of therapies for patients with immune-mediated diseases.

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

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

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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.

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

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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.

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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

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