Project description:Innate Lymphoid cells (ILCs) are a group of tissue resident lymphocytes that participate in immune defense and tissue homeostasis. The existence and ontogeny of ILCs during zebrafish embryonic development are not defined. During embryogenesis, hematopoietic stem cells (HSCs) and HSC-independent Progenitor Cells (HPCs) form contemporaneously and produce overlapping and distinct immune cell types. To delineate when ILCs emerge and if they originate exclusively from HSCs or HPCs, we performed lineage tracing of the emerging hematopoietic system during larval development followed by single cell RNA sequencing of HSC and HPC progeny. To determine if the ILC-like cells are derived from the definitive hematopoietic wave, we did lineage tracing and scRNA-seq experiment in runx1W84X mutants and illustrated that all ILC-like clusters are Runx1-dependent. We confirmed that the transcriptionally detected larval ILC-like cells are Rag-independent and Il2rg-dependent. Lastly, embryonic ILCs are functional because they respond to an immune system stimulation with a viral mimic. The work provides fundamental knowledge on the early establishment of immune hierarchies and opens the zebrafish model to the exploration of ILC origination and function.
Project description:We identified a new type of bone marrow progenitors termed early innate lymphoid cell progenitor (EILP) using TCF-1 GFP reporter mice. We compared the transcriptomes of early innate lymphoid cell progenitors (EILP) with other early progenitors, including HSC, LMPP, CMP, CLP, ETP and DN3.
Project description:Innate lymphoid cells (ILC) in the small intestine govern immune homeostasis and protect the host against gut pathogens. While distinct cell-intrinsic signals have been identified that determine ILC development and differentiation, it has remained unclear which cell population regulates ILC sustenance. Using unbiased single cell RNA transcriptomic analysis of intestinal fibroblasts, we have identified a specialized Ccl19-expressing fibroblastic reticular cell (FRC) population that underpins solitary intestinal lymphoid tissue (SILT) structures including cryptopatches and isolated lymphoid follicles. Conditional ablation of lymphotoxin-β receptor (LTβR) signalling in SILT FRC impeded the maturation of isolated lymphoid follicles and blocked ILC maintenance through the downregulation of IL-7, consequently resulting in the elevated susceptibility to bacterial infection. Moreover, specific Ltbr ablation in FRC during adulthood revealed that constant LTβR-dependent FRC-ILC interaction is required to maintain SILT structures and ILC populations. Taken together, our study unveils a critical intestinal FRC niche that secures protective gut immunity.
Project description:Drosophila larval ventral nerve cord (VNC) shares many similarities with the spinal cord of vertebrates and has emerged as a major model for understanding the development and function of motor systems. We use high quality single cell RNA sequencing to create a comprehensive atlas of larval VNC cell types. Our atlas provides a high-resolution characterization of larval VNC capturing primary neurons, glia and the functional landscape that coordinates larval behavior. At the same time, this atlas offers unique insights into neurogenesis and into the strategies and signaling networks utilized for generation of the adult VNC.
Project description:Natural Killer (NK) cells at different developmental stages (common lymphoid progenitor (CLP), innate lymphoid cell progenitors (ILCP), and refined NK progenitor (NKP)) were collected from Vav1+iCre FOXO1,3flox/flox mice (C57BL/6 background). Total RNA was harvested and sequenced with a strand-specific paired-end RNA-seq protocol.
Project description:Purpose: Regulome analysis of skin innate lymphoid cells Methods: Innate lymphoid cells were sorted from epidermis, dermis and subcutis of adult B6 mice, respectively and subjected to transposition reaction and library preparation. Results: 20,869 accessible regulatory elements were detected Conclusions: This study reveals regulome landscape of skin innate lymphoid cells
Project description:Purpose: Transcriptomic analysis of skin innate lymphoid cells Methods: Innate lymphoid cells were sorted from epidermis, dermis and subcutis of adult B6 mice, respectively and subjected to RNA isolation and library preparation. Results: 3,078 differentially expressed genes (fold change>2 and p-value<0.05) were detected Conclusions: This study reveals transcriptome landscape of skin innate lymphoid cells