Ontology highlight
ABSTRACT:
PROVIDER: PRJNA484655 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7646690_1.fastq.gz | Fastqsanger.gz | |||
| SRR7646690_2.fastq.gz | Fastqsanger.gz | |||
| SRR7646700_1.fastq.gz | Fastqsanger.gz | |||
| SRR7646700_2.fastq.gz | Fastqsanger.gz | |||
| SRR7646710_1.fastq.gz | Fastqsanger.gz |
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Project description:Rna sequencing of purified human group 3 innate lymphoid cells from non-reactive lymph nodes and spleen, inflamed tonsils and peripheral blood.
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Project description:Group 3 innate lymphoid cells (ILC3) are defined by the expression of RORM-NM-3t, which is selectively required for their development. The lineage-specified progenitor cells of human ILC3 and their developmental site after birth remain undefined. Here we identified a novel population of human CD34+ hematopoietic progenitor cells (HPC) expressing RORM-NM-3t and sharing with ILC3 a distinct transcriptional signature. RORM-NM-3t+ CD34+ HPC were located in tonsils and intestinal lamina propria (LP) and selectively differentiated towards ILC3. Conversely, RORM-NM-3t- CD34+ HPC displayed commitment potential for both ILC3 and NK cells and the differentiation fate towards these two cell lineages was determined by cytokine and aryl hydrocarbon receptor (AhR) signaling. Thus, we propose that RORM-NM-3t+ CD34+ cells represent human lineage-specified progenitors of IL-22+ ILC3 and that tonsils as well as intestinal LP might be preferential sites of their differentiation. ILC3, NK cells and the CD34+ HPC subsets were sorted from tonsils of 6 distinct donors to purity above 95%. cRNA of the sorted cell populations was hybridized to an Agilent Whole Human Genome Oligo Microarrays (8x60K v2, Design ID 039494)
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Project description:Innate lymphoid cells (ILCs) serve as sentinels in mucosal tissues, sensing release of soluble inflammatory mediators, rapidly communicating danger via cytokine secretion, and functioning as guardians of tissue homeostasis. Although ILCs have been studied extensively in model organisms, little is known about these âfirst respondersâ in humans, especially their lineage and functional kinships to cytokine-secreting T helper cell (Th) counterparts. Here, we report gene regulatory circuitries for four human ILCâTh counterparts derived from mucosal environments, revealing that each ILC subset diverges as a distinct lineage from Th and circulating natural killer cells, but shares circuitry devoted to functional polarization with their Th counterparts. Super-enhancers demarcate cohorts of cell identity genes in each lineage, uncovering new modes of regulation for signature cytokines, novel molecules that likely impart important functions to ILCs, and potential mechanisms for autoimmune disease SNP associations within ILCâTh subsets. Molecular profiling of innate lymphoid and T helper cells subsets purified from tonsils and NK cells purified from peripheral blood using Assay for Transposase-Accessible Chromatin (ATAC) and chromatin immunoprecipitation (H3K4me3 and H3K27ac).
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Project description:Single-cell deciphering of human fetal innate lymphoid cell development
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Project description:Palatine tonsils are secondary lymphoid organs that are strategically positioned in the oropharynx to secure a first line of defense against oral pathogens. Specialized immune-interacting fibroblasts, generally termed fibroblastic reticular cells (FRC), underpin distinct microenvironments within lymphoid organs to compartmentalize and direct the efficient interaction and activation of immune cells. As a particular anatomical property, palatine tonsils harbor a reticular-shaped lymphoepithelium that generates an antigen sampling zone in the crypts. While the histological ultrastructure and the immune cell composition of human palatine tonsils has been elaborated in detail, the molecular identity of the diverse stromal cell compartments including FRC and the specialized lymphoepithelium remains largely unknown. Here, we have employed single cell transcriptomics and extensive flow cytometric analyses to unveil the molecular identity of tonsillar cells and to disentangle the heterogeneity of fibroblast and epithelial cell subsets in palatine tonsils. Our results reveal a remarkable conservation of stromal cell organization and molecularly-defined subsets in infant and adult human palatine tonsils.
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Project description:Group 3 innate lymphoid cells (ILC3) are defined by the expression of RORγt, which is selectively required for their development. The lineage-specified progenitor cells of human ILC3 and their developmental site after birth remain undefined. Here we identified a novel population of human CD34+ hematopoietic progenitor cells (HPC) expressing RORγt and sharing with ILC3 a distinct transcriptional signature. RORγt+ CD34+ HPC were located in tonsils and intestinal lamina propria (LP) and selectively differentiated towards ILC3. Conversely, RORγt- CD34+ HPC displayed commitment potential for both ILC3 and NK cells and the differentiation fate towards these two cell lineages was determined by cytokine and aryl hydrocarbon receptor (AhR) signaling. Thus, we propose that RORγt+ CD34+ cells represent human lineage-specified progenitors of IL-22+ ILC3 and that tonsils as well as intestinal LP might be preferential sites of their differentiation.
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