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B cells and their progenitors reside in homeostatic meninges

ABSTRACT: B cells and their progenitors reside in homeostatic meninges

PROVIDER: PRJNA693439 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13488709.fastq.gz	Fastqsanger.gz
	SRR13488710.fastq.gz	Fastqsanger.gz
	SRR13488711.fastq.gz	Fastqsanger.gz
	SRR13488712.fastq.gz	Fastqsanger.gz
	SRR13488713.fastq.gz	Fastqsanger.gz

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B cells and their progenitors reside in homeostatic meninges

Project description:The central nervous system (CNS) is ensheathed by the meninges and cerebrospinal fluid. Recent findings suggest complex immunological functions of these CNS-associated border tissues. Unlike myeloid lineage cells, lymphocytes in border compartments have been largely disregarded in previous studies. Based on single cell transcriptomics, we here identified a highly location-specific composition and expression profile of tissue-resident leukocytes in every border compartment. Only the dura layer of the meninges contained a large population of B cells under homeostatic conditions in multiple species. Murine dura B cells exhibited slow turnover, long-term tissue residency and matured in experimental neuroinflammation. The dura also contained B lineage progenitors at the pro-B cell stage unexpected outside of bone marrow, without direct influx from the periphery or the skull bone marrow. This identifies the dura as an unexpected site of B cell residence and potentially development in homeostasis and neuroinflammation.

2021-05-01 | GSE165153 | GEO

CNS antigen-specific control of early B-lineage development in the meninges

Project description:In this work we report that early developing B cells present in the meninges of mice at all ages. Single cell RNA-sequencing (scRNA-seq) analysis revealed a consecutive trajectory of meningeal developing B cells in mice and non-human primates (NHPs). Parabiosis together with lineage tracing of hematopoietic stem cells (HSCs) showed that meningeal developing B cells are continuously replenished from the HSC-derived progenitors via a circulation-independent route. Importantly, autoreactive immature B cells which recognize myelin oligodendrocyte glycoprotein (MOG), a central nervous system (CNS)-specific antigen, are eliminated from the meninges but not BM. Furthermore, genetic deletion of MOG tolerated the development/presence/residence of self-reactive B cells in the meninges. Thus, we propose that meninges function as a unique reservoir for B cell development, allowing in situ negative selection of CNS-antigen-autoreactive B cell clones to ensure a local non-self-reactive immune repertoire.

2021-11-01 | GSE176263 | GEO

Effect of DSS Colitis on Meninges

Project description:The Meninges of mice which were treated with DSS to induce colitus were compared to control mice.

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Bacteria hijack a neuro-immune axis in meninges to facilitate brain invasion

Project description:The meninges are densely innervated by nociceptive sensory neurons that mediate pain and headache. How pain and neuro-immune interactions impact meningeal host defenses is unclear. Bacterial meningitis causes life-threatening infections of the meninges and central nervous system (CNS), affecting over one million people a year. Here we find that Nav1.8+ neuron signaling to immune cells in the meninges via the neuropeptide calcitonin gene-related peptide (CGRP) exacerbates bacterial meningitis. Nociceptor ablation reduced meningeal and brain invasion by two bacterial pathogens: Streptococcus pneumoniae and Streptococcus agalactiae. S. pneumoniae activated nociceptors via Pneumolysin to release CGRP, which acts through its receptor RAMP1 on meningeal macrophages to inhibit chemokine expression, neutrophil recruitment and antimicrobial defenses. Macrophage-specific RAMP1 deficiency or blockade of RAMP1 signaling enhanced immune responses and bacterial clearance in meninges and brain. Therefore, targeting a neuro-immune axis in the meninges can enhance host defenses and may be a potential treatment for bacterial meningitis.

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Meninges from mice with different microbiomes

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Nestin- and doublecortin-positive cells reside in adult spinal cord meninges and participate in injury-induced parenchymal reaction.

Project description:Adult spinal cord has little regenerative potential, thus limiting patient recovery following injury. In this study, we describe a new population of cells resident in the adult rat spinal cord meninges that express the neural stem/precursor markers nestin and doublecortin. Furthermore, from dissociated meningeal tissue a neural stem cell population was cultured in vitro and subsequently shown to differentiate into functional neurons or mature oligodendrocytes. Proliferation rate and number of nestin- and doublecortin-positive cells increased in vivo in meninges following spinal cord injury. By using a lentivirus-labeling approach, we show that meningeal cells, including nestin- and doublecortin-positive cells, migrate in the spinal cord parenchyma and contribute to the glial scar formation. Our data emphasize the multiple roles of meninges in the reaction of the parenchyma to trauma and indicate for the first time that spinal cord meninges are potential niches harboring stem/precursor cells that can be activated by injury. Meninges may be considered as a new source of adult stem/precursor cells to be further tested for use in regenerative medicine applied to neurological disorders, including repair from spinal cord injury.

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Identification of Mfn2 interacting proteins in homeostatic endothelial cells

Project description:Identification of Mfn2 interacting proteins in homeostatic endothelial cells using affinity purification-mass spectrometry analysis.

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Single cell transcriptomic analyses of the developing meninges reveal meningeal fibroblast diversity and function

Project description:The meninges are a multilayered structure composed of fibroblasts, blood and lymphatic vessels, and immune cells. Meningeal fibroblasts secrete a variety of factors that control CNS development, yet strikingly little is known about their heterogeneity or development. Using single cell sequencing, we report distinct transcriptional signatures for fibroblasts in the embryonic dura, arachnoid and pial. We define new markers for meningeal layers and show conservation in human meninges. We find that embryonic meningeal fibroblasts are transcriptionally distinct between brain regions and identify a regionally localized pial sub-population marked by expression of µ-Crystallin. Developmental analysis reveals a progressive, ventral to dorsal maturation of telencephalic meninges. Our studies present an unprecedented view of meningeal fibroblasts, providing a molecular profile of embryonic meningeal fibroblasts by layer that yield insights into mechanisms of meninges development and function.

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Meninges from mice with different microbiomes

Project description:Meninges from mice with different microbiomes

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Effect of DSS Colitis on Meninges

Project description:Effect of DSS Colitis on Meninges

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