Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Clonal CD8+ T Cells Populate the Leptomeninges and Coordinate with Immune Cells in Human Degenerative Brain Diseases

ABSTRACT: Meningeal immune cells monitor the central nervous system (CNS) and influence neuroinflammation in mice, but the human leptomeningeal immune landscape and the changes that occur in this immunological niche in neurodegeneration remain underexplored. We performed single-cell RNA and T cell receptor (TCR) sequencing of 99,625 high-quality immune cells from 57 leptomeninges and brain samples from donors with Alzheimer’s disease (AD), amyotrophic lateral sclerosis, and Parkinson’s disease and found that while the leptomeninges are home to highly clonally expanded CD8 tissue-resident memory (TRM) T cells, the maximal level of clonal expansion was decreased in AD in comparison to non-neurodegenerative controls. Intra-patient paired tissue analysis further revealed that brain and leptomeningeal TCR repertoires share significant similarities, but tissue-specific clones emerge in AD. Finally in AD, the degree of CD8 TRM clonal expansion was positively correlated with microglial TGFB2, suggesting that brain and leptomeningeal immune cells coordinate their activities in AD. In addition to identifying key inflammatory dynamics in the human degenerating CNS, this study establishes a foundational resource for future studies that could inform treatment for AD and other neuroinflammatory diseases.

ORGANISM(S): Homo sapiens

PROVIDER: GSE288856 | GEO | 2025/11/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Gene expression profile at single cell level of YS-derived cells and monocyte-derived cells from brain parenchyma and leptomeninges of Ms4a3-Cre: R26-TdTomato: Cx3cr1-gfp mice

Project description:Ms4a3-Cre: R26-TdTomato: Cx3cr1-gfp mice allow discrimination between YS-derivd and monocyte-derived macrophages in the brain parenchyma and leptomeninges by color. We used single cell RNAseq for RNA profiling to compare YS-derived micrglia, monocyte-derived microglia, YS-derived leptomeningeal macrophages, and monocyte-derived leptomeningeal macrophages.

2024-12-02 | GSE282946 | GEO

Single-nucleus RNA sequencing of human fetal leptomeninges

Project description:To investigate the development of human leptomeninges and their co-development with the brain. Nuclei were extracted from eight human fetal leptomeninges obtained from aborted embryos, ranging from PCW8 to PCW21 (post-conceptional weeks). The entire arachnoid mater, pia mater, associated blood vessels, and immune cells were included for single-nucleus RNA sequencing (snRNA-seq).

2025-03-01 | GSE276537 | GEO

Single cell approaches define the murine leptomeninges:cortical brain interface as a distinct cellular neighborhood comprised of neural and nonneural cell types

Project description:The interface between the brain surface and the adjacent meninges is a selective barrier regulating fluid, protein and immune cell exchange between the CNS and periphery. However, the cell types that form this important interface are not yet fully defined. To address this limitation, we have used single cell RNA-sequencing (scRNA-seq) and single cell spatial transcriptomics together with morphological lineage tracing and immunostaining to analyze the adult murine cortex. We show that the cortical interface is comprised of three major cell types, leptomeningeal cells, border astrocytes and tissue-resident macrophages. On the peripheral side the interface is comprised of transcriptionally-distinct PDGFRα-positive leptomeningeal mesenchymal cells that are intermingled with macrophages. This leptomeningeal pial layer is lined by a population of transcriptionally-distinct border astrocytes. The interface neighborhood is rich in growth factor mRNAs, including many leptomeningeal ligands predicted to act on both the border astrocytes and macrophages. On the CNS side of the interface is the relatively cellsparse cortical layer one containing interneurons, microglia, parenchymal astrocytes, oligodendrocyte precursor cells and oligodendrocytes. Except for the border astrocytes, layer one cells are not closely-associated with the interface, suggesting that secreted ligands may be the major way the brain interface communicates with the underlying cortical parenchyma. Thus, our data provide a molecular/cellular resource describing the brain interface cell types and their interactions, thereby enabling future studies asking how this distinct cellular compartment regulates CNS:periphery interactions.

2025-08-01 | GSE296134 | GEO

Single cell approaches define the murine leptomeninges:cortical brain interface as a distinct cellular neighborhood comprised of neural and nonneural cell types

2025-08-01 | GSE297616 | GEO

RNA Sequencing of sorted CD31+ meningeal endothelial cells from naïve Lewis rats

Project description:The meninges, comprising the leptomeninges (pia and arachnoid layers) and the pachymeninx (dura layer), participate in CNS autoimmunity but their relative contributions remain unclear. Here, we report on findings in animal models of CNS autoimmunity and in multiple sclerosis patients, where, in chronic disease, the leptomeninges were highly inflamed and showed structural changes, while the dura mater was only marginally affected. Although dural vessels were leakier than leptomeningeal vessels, effector T cells adhered more weakly to the dural endothelium. Furthermore, local antigen presenting cells presented myelin and neuronal autoantigens less efficiently and the activation of autoreactive T cells was lower in dural than leptomeningeal layers, preventing local inflammatory processes. Direct antigen application was required to evoke a local inflammatory response in the dura. Together, our data demonstrate an uneven involvement of the meningeal layers in CNS autoimmunity, in which effector T cell trafficking and activation are functionally confined to the leptomeninges, while the dura remains largely shielded from CNS autoimmune processes.

2022-07-04 | GSE203046 | GEO

Adult Leptomeninges are Regionally Patterned and Provide Specialized Support to Underlying Brain Tissue

Project description:The leptomeninges envelop the central nervous system and contribute to brain homeostasis by producing trophic factors and regulating entrance of cells, factors and agents, immune responses and cerebrospinal fluid production. We report that leptomeninges from adult mice are regionally patterned. Leptomeninges dissected from anterior or posterior aspects of the forebrain grown in hetero- or homo-typic culture with anterior and posterior cortical cells demonstrate differences in ability to support survival of neuronal subsets and proliferation of progenitors for astrocytes and oligodendrocytes. Meningeal support changes with age: co-culture with 18-month old leptomeninges reduced numbers of cortical progenitor cells and neurons but increased astrocyte expansion. Analysis of cytokine secretion and single cell RNA-sequencing revealed differences in anterior versus posterior, young versus old meningeal factors and composition. These data demonstrate that adult leptomeninges are regionally patterned in cell composition and functional properties, and suggest that meningeal deficits may contribute to brain aging and disease.

2021-11-01 | GSE139922 | GEO

Single-cell sequencing of tissue-resident CD4+ T cells that drive compartmentalized immunopathology in the CNS

Project description:In chronic inflammatory diseases of the central nervous system (CNS), immune cells persisting behind the blood-brain barrier are supposed to promulgate local tissue destruction. The drivers of such compartmentalized inflammation remain unclear, but tissue-resident memory T cells (TRM) represent a potentially important cellular player in this process

2022-02-19 | E-MTAB-11422 | biostudies-arrayexpress

Single-cell sequencing of tissue-resident CD8+ T cells that drive compartmentalized immunopathology in the CNS

2022-03-14 | E-MTAB-11511 | biostudies-arrayexpress

Single-cell atlas of mouse leptomeningeal immune cells

Project description:Metastasis to the cerebrospinal fluid (CSF)-filled leptomeninges, or leptomeningeal metastasis (LM), represents a fatal complication of cancer. Proteomic and transcriptomic analyses of human CSF reveal a substantial inflammatory infiltrate in LM. We find the solute and immune composition of CSF in the setting of LM changes dramatically, with notable enrichment in IFN-gamma signaling. To investigate the mechanistic relationships between immune cell signaling and cancer cells within the leptomeninges, we developed syngeneic lung, breast, and melanoma LM mouse models. We find that transgenic host mice, lacking IFN-gamma or its receptor, fail to control LM growth. Overexpression of Ifng through a targeted AAV system controls cancer cell growth independent of adaptive immunity. Instead, leptomeningeal IFN-gamma actively recruits and activates peripheral myeloid cells, generating a diverse spectrum of dendritic cell subsets. These migratory, CCR7+ dendritic cells orchestrate the influx, proliferation, and cytotoxic action of natural killer cells to control cancer cell growth in the leptomeninges. This work uncovers leptomeningeal-specific IFN-gamma signaling and suggests a novel immune-therapeutic approach against tumors within this space.

2023-03-27 | GSE221593 | GEO

Transcriptome of mouse leptomeningeal fibroblats

Project description:Meninges, or the membranous coverings of the brain and spinal cord, play host to dozens of morbid pathologies. In this study we provide a method to isolate the leptomeningeal cell layer, identify leptomeninges in histologic slides, and maintain leptomeningeal fibroblasts in in vitro culture. Using an array of transcriptomic, histological, and cytometric analyses, we identified ICAM1 and SLC38A2 as two novel markers of leptomeningeal cells in vivo and in vitro. Our results confirm the fibroblastoid nature of leptomeningeal cells and their ability to form a sheet-like layer that covers the brain and spine parenchyma. These findings will enable researchers in central nervous system barriers to describe leptomeningeal cell functions in health and disease.

2021-09-29 | GSE150419 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data