Brain-infiltrating ILC2s-derived alpha-calcitonin gene-related peptide promoting angiogenic sprouting accelerates post-stroke angiogenesis
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PROVIDER: PRJNA1294141 | ENA |
REPOSITORIES: ENA
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Project description:Group 2 innate lymphoid cells (ILC2s) are key players in immune regulation and tissue repair in barrier immunity, but they are rarely seen in the brain. Since ILC2s can be intrinsically expanded by IL2/IL2 antibody complex, we investigated the transcriptomic changes induced by IL2/IL2 antibody complex (IL2-JES6-1) after ischemic stroke, we performed single-cell RNA sequencing of the CD45high immune cells from the infarcted hemisphere at day 14 after MCAO using 10x Genomics scRNAseq. To investigate the key mechanism of ILC2s-mediated long-term recovery after ischemic stroke, we performed single-cell RNA sequencing of the infarcted hemisphere at day 14 after MCAO using 10x Genomics scRNAseq.
2025-07-23 | GSE303092 | GEO
Project description:Age-related macular degeneration (AMD) is a global leading cause of visual impairment in older populations. ‘Wet’ AMD, the most common subtype of this disease, occurs when pathological angiogenesis infiltrates the subretinal space (choroidal neovascularization), causing hemorrhage and retinal damage. Gold standard anti-vascular endothelial growth factor (VEGF) treatment is an effective therapy, but the long-term prevention of visual decline has not been as successful. This warrants the need to elucidate potential VEGF-independent pathways. We generated blood out-growth endothelial cells (BOECs) from wet AMD and normal control subjects, then induced angiogenic sprouting of BOECs using a fibrin gel bead assay. To deconvolute endothelial heterogeneity, we performed single-cell transcriptomic analysis on the sprouting BOECs, revealing a spectrum of cell states. Our wet AMD BOECs share common pathways with choroidal neovascularization such as extracellular matrix remodeling that promoted proangiogenic phenotype, and our ‘activated’ BOEC subpopulation demonstrated proinflammatory hallmarks, resembling the tip-like cells in vivo. We uncovered new molecular insights that pathological angiogenesis in wet AMD BOECs could also be driven by interleukin signaling and amino acid metabolism. A web-based visualization of the sprouting BOEC single-cell transcriptome (https://christinecheunglab.shinyapps.io/human_wet_AMD_sprouting/) has been created to facilitate further discovery research.
2022-11-02 | GSE213933 | GEO
Project description:Identifying new markers of angiogenic sprouting using transcriptomics: New role for RND3
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Project description:Neuroimmune interactions have emerged as critical modulators of allergic inflammation, and type 2 innate lymphoid cells (ILC2s) are an important cell type for mediating these interactions. Here, we show that ILC2s expressed both the neuropeptide CGRP (Calcitonin Gene-Related Peptide) and its receptor. CGRP potently inhibited alarmin-driven type 2 cytokine production and proliferation by lung ILC2s both in vitro and in vivo. CGRP induced marked changes in ILC2 expression programs in vivo and in vitro, attenuating alarmin-driven proliferative and effector responses. A distinct subset of ILCs scored highly for a CGRP-specific gene signature after in vivo alarmin stimulation, suggesting CGRP regulated this response. Finally, we observed increased ILC2 proliferation and type 2 cytokine production and exaggerated responses to alarmins in mice lacking the CGRP receptor. Together, these data indicate that endogenous CGRP is a critical negative regulator of ILC2 responses in vivo.
2019-10-08 | GSE136154 | GEO
Project description:Group 2 innate lymphoid cells (ILC2s) in the lung are stimulated by inhaled allergens. ILC2s do not directly recognize allergens but they are stimulated by cytokines including interleukin (IL)-33 released by damaged epithelium.Lung ILC2s, upon stimulation, produce T helper 2 cell-type cytokines inducing T cell independent allergic lung inflammation. We now report that lung ILC2s, upon activation by an allergen or IL-33, acquire the properties of memory cells. The activated ILC2s initially proliferate and secrete cytokines, followed by a contraction phase as they stop producing cytokines. Nevertheless, some persist long after the resolution of the inflammation and acquire intrinsic capacities to react to unrelated allergens more vigorously than naïve ILC2s, thus mediating a severe allergic lung inflammation. Gene expression profiles of the previously activated ILC2s show a gene signature of memory T cells. These antigen non-specific memory ILC2s may explain why asthma patients are often sensitized to multiple allergens. ILC2s were isolated from mouse lungs from naive and IL-33 injected mice 4 days, 14 days and 4 months after the initial treatment. RNA was extracted from those ILC2 populations and analyzed for gene expression profiles. RNA was also extracted from ILC2s isolated from lung draining mediastinal lymph node (mLN) 4 days and 14 days after IL-33 treatment.
2016-06-30 | E-GEOD-81700 | biostudies-arrayexpress
Project description:Several environmental pollutants have been reported to exhibit either pro-angiogenic or anti-angiogenic effects, which may contribute to related vascular diseases. However, the specific mechanism by which pollutants induce sprouting angiogenesis is unclear, and there are few studies on the association between the site of hyperangiogenesis and vascular diseases. In this study, zebrafish were exposed to bisphenol S (BPS, 1~100 µg/L) and tetrabromobisphenol S (TBBPS, 0.1 and 10 µg/L) from the embryonic to the larval stage to investigate how pollutants interfere with the function of ectopic sprouting vessels. Results showed that BPS and TBBPS promoted ectopic sprouting angiogenesis in different types of vascular plexus at different developmental time points but inhibited vascular endothelial-cadherin (VE-cadherin) expression. The proteomic analyses on eGFP-positive endothelial cells isolated from Tg(flk1: eGFP) zebrafish indicated that both BPS and TBBPS induced ectopic angiogenesis through inhibiting VE-cadherin-mediated adherens junction and activating the downstream pro-angiogenic signaling. In ectopic sprouting vessels induced by BPS and TBBPS, an increased endothelial permeability resulted in white blood cells recruitment and erythrocyte retention. Human oxidized lipids were also prone to deposit in these ectopic vessels following BPS and TBBPS exposure. This suggests that ectopic angiogenesis is a cause of vascular dysfunction and related diseases.
2024-11-12 | PXD057764 |
Project description:Angiogenesis-inhibitor (AI) drugs targeting vascular endothelial growth factor (VEGF) signalling to the endothelial cell (EC) are used to treat various cancers types. However, primary or secondary resistance to therapy is common. Clinical and pre-clinical studies suggest that other alternative pro-angiogenic factors are up-regulated after VEGF-pathway inhibition. Therefore, identification alternative pro-angiogenic pathway(s) is critical for the development of more effective anti-angiogenic therapy. Here we study the role of apelin as a pro-angiogenic G-protein coupled receptor (GPCR) ligand in tumor growth and angiogenesis. We applied single-cell RNA-sequencing to Mouse Lewis lung carcinoma (LLC1) or B16F10 mouse melanoma cell lines (1 X 106) implanted subcutaneously into the flanks of 12 weeks old Apln-/y or littermate control mice in combination with sunitinib or control (vehicle) treatment. We found apelin loss reduced angiogenic sprouting and tip cell marker gene expression in comparison to the sunitinib-alone treated mice and prevented EC tip cell differentiation.
2023-04-06 | E-MTAB-11663 | biostudies-arrayexpress
Project description:Dysfunction of group II innate lymphoid cells (ILC2s) plays an important role in the development of type II inflammation-related diseases such as asthma and pulmonary fibrosis. Notably, neural signals are increasingly recognized as pivotal regulators of ILC2s. However, how ILC2s intrinsically modulate their responsiveness to these neural signals is still largely unknown. Here, using single-cell RNA sequencing and bulk mRNA sequencing, we report that the immune regulatory molecule PAC1 (phosphatase of activated cells 1) selectively promotes the signaling of neuropeptide CGRP (calcitonin gene-related peptide) in ILC2s. Moreover, PAC1 is necessary for ensuring the expression of CGRP-response genes by influencing chromatin accessibility. In summary, our study demonstrates that PAC1 is an important regulator of ILC2 responses and we propose that PAC1 is a potential target for therapeutic interventions of type II inflammation-related diseases.
2024-09-29 | GSE272724 | GEO
Project description:Dysfunction of group II innate lymphoid cells (ILC2s) plays an important role in the development of type II inflammation-related diseases such as asthma and pulmonary fibrosis. Notably, neural signals are increasingly recognized as pivotal regulators of ILC2s. However, how ILC2s intrinsically modulate their responsiveness to these neural signals is still largely unknown. Here, using single-cell RNA sequencing and bulk mRNA sequencing, we report that the immune regulatory molecule PAC1 (phosphatase of activated cells 1) selectively promotes the signaling of neuropeptide CGRP (calcitonin gene-related peptide) in ILC2s. Moreover, PAC1 is necessary for ensuring the expression of CGRP-response genes by influencing chromatin accessibility. In summary, our study demonstrates that PAC1 is an important regulator of ILC2 responses and we propose that PAC1 is a potential target for therapeutic interventions of type II inflammation-related diseases.
2024-09-29 | GSE272723 | GEO