Venous plexus-associated lymphoid hubs support meningeal humoral immunity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1064095 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27504500_1.fastq.gz | Fastqsanger.gz | |||
| SRR27504500_2.fastq.gz | Fastqsanger.gz | |||
| SRR27504501_1.fastq.gz | Fastqsanger.gz | |||
| SRR27504501_2.fastq.gz | Fastqsanger.gz | |||
| SRR27504502_1.fastq.gz | Fastqsanger.gz |
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Project description:Venous plexus-associated lymphoid hubs support meningeal humoral immunity
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Project description:There is increasing interest in how immune cells in the meninges, the membranes that surround the brain and spinal cord, contribute to homeostasis and disease in the central nervous system (CNS)1,2. The outer layer of meninges, the dura mater, has recently been described to contain both innate and adaptive immune cells, and function as a site for B cell development. Here, we identified organised lymphoid structures protecting fenestrated vasculature in the dura mater that we term dural-associated lymphoid tissue (DALT). We found the most elaborate immune organization, including lymphatic vessels, surrounding the rostral_x0002_rhinal confluence of sinuses. We termed this structure that interfaced with the skull bone marrow and a comparable venous plexus at the skull base, the rostral-rhinal venolymphatic hub. Immune aggregates were present in DALT during homeostasis and expanded with age or following challenge with systemic or nasal antigens. DALT contained germinal centre (GC) B cells, and supported the generation of somatically mutated, antibody-producing cells in response to a nasal pathogen challenge. Inhibition of lymphocyte entry into the rostral-rhinal hub at the time of nasal viral challenge abrogated the generation of germinal centre B cells and class-switched plasma cells, as did perturbation of B-T cell interactions. These data demonstrate lymphoid architecture around vasculature in dura mater that can sample antigens and rapidly support humoral immune responses following local pathogen challenge.
2024-03-04 | GSE254265 | GEO
Project description:We have identified previously unappreciated dural-associated lymphoid tissue hubs, present in homeostasis, and anatomically poised to acquire local and systemic antigens. These venolymphatic hubs facilitate rapid expansion of antigen specific immune responses and likely help defend the underlying CNS parenchyma against foreign invaders.
2024-01-15 | GSE253135 | GEO
Project description:The cellular evolutions and molecular programs underlying the arteriovenous fate settling of embryonic vascular endothelial cells (ECs) are critical for understanding arteriogenesis and inspiring new approaches for regenerative biology. Using different strategies of single-cell RNA sequencing, we constructed the transcriptional landscape of early arteriovenous EC development in both mouse and human embryos, demonstrating the evolutionary conservation of principal vascular EC types and providing a series of conserved arteriovenous genes. We showed an unexpected diversity of arteriovenous characteristics in morphologically alike vascular plexus and further uncovered two transcriptomically distinct arterial EC types, whereas most of heterologous ligand-receptor pairs were shared by different arterial vasculatures. By computational predicting and further genetic lineage tracing, we revealed the widespread venous arterialization in the mid-gestational mouse embryo proper. Interestingly, we demonstrated at transcriptomic level that Notch1 was dispensable for venous arterialization but required subsequently for the arterial feature strengthening in the arterial plexus ECs. Altogether, our findings unprecedentedly detail the comprehensive single-cell mapping of early embryonic vascular ECs in vivo, decipher an asymmetric arteriovenous characteristics different than that in adults, and reveal an extensive venous-to-arterial fate conversion in the vascular plexus.
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Project description:Repair of the pulmonary vascular bed and the origin of new vasculature remains underexplored despite the critical necessity to meet oxygen demands after injury. Given their critical role in angiogenesis in other settings, we investigated the role of venous endothelial cells in endothelial regeneration after adult lung injury. Using single cell transcriptomics, we identified the norepinephrine transporter Slc6a2 as a marker of pulmonary venous endothelial cells and targeted that locus to generate a venous-specific, inducible Cre mouse line. Contributions of the venous endothelial cells to angiogenesis were examined during postnatal development, adult viral injury, and adult hyperoxia injury. Remarkably, we observed that venous endothelial cells proliferate into the adjacent capillary bed upon influenza injury and hyperoxia injury, but not during normal postnatal development. Imaging analysis demonstrated that venous endothelial cells exhibit the ability to proliferate and differentiate into general capillary and CAR4 expressing aerocyte capillary endothelial cells after infection, thus contributing to repair of the capillary plexus vital for gas exchange. Single cell transcriptomic analysis of Slc6a2 lineage traced cells confirmed these observations, with progeny exhibiting significant loss of venous identity and gain of capillary marker expression upon injury resolution. Our studies thus establish that venous endothelial cells exhibit demonstrable progenitor capacity upon respiratory viral injury and sterile injury, contributing to repair of the alveolar capillary bed responsible for pulmonary function.
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Project description:Gene expression profiles generated from human tumor cells laser-microdissected from surgical samples of seven choroid plexus papillomas (Grade I WHO) as eight samples of epithelial cells lasermicrodissected from normal choroid plexus obtained at autopsy. Choroid plexus tumors are rare pediatric brain tumors derrived from the choroid plexus epithelium. Gene expression profiles of lasermicrodissected tumor cells from 7 individual choroid plexus tumor samples obtained at surgery were compared to gene expression profiles from non-neoplastic choroid plexus epithelial cells lasermicrodissected from normal non-neoplastic choroid plexus obtained at autopsy (Am J Surg Pathol. 2006 Jan;30(1):66-74.) in order to identfy genes differentially expressed in choroid plexus tumor cells.
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Project description:Gene expression data from normal mouse choroid plexus, choroid plexus papilloma and choroid plexus carcinoma
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Project description:Choroid plexus secretes cerebrospinal fluid important for brain development and homeostasis. The OTX2 homeoprotein is critical for choroid plexus development and remains highly expressed in adult choroid plexus. Through RNA sequencing analyses of constitutive and conditional knockdown adult mouse models, we reveal putative roles for OTX2 in choroid plexus function, including cell signaling and adhesion, and show that it regulates the expression of factors secreted into cerebrospinal fluid, notably transthyretin. We also show that Otx2 expression impacts choroid plexus immune and stress responses, and also affects splicing which leads to changes in mRNA isoforms of proteins implicated in oxidative stress response and DNA repair. Through mass spectrometry analysis of OTX2 protein partners in the choroid plexus, and in known non-cell autonomous target regions such as visual cortex and subventricular zone, we identified putative targets involved in cell adhesion, chromatin structure and RNA processing. Thus, OTX2 retains important roles in choroid plexus function and brain homeostasis throughout life.
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