Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell RNA sequencing reveals tissue-associated fibroblastic reticular cell heterogeneity in human secondary lymphoid organs

ABSTRACT: Fibroblastic reticular cells (FRCs) actively support secondary lymphoid organ (SLO) architecture. They regulate innate and adaptive immunity by compartmentalizing immune cells in specialized niches, and tightly interacting with them. The phenotypic and functional diversity of FRCs in human SLOs remains largely uncharacterized. We performed a comprehensive profiling of FRCs by single-cell RNA sequencing on human tonsils and lymph nodes. We provide the first complete description of the tonsillar CD45-negative compartment. We identified and validated in tonsil, a population of follicular dendritic cells restricted to the mantle zone and discovered two CCL21-negative FRC subsets intermingling with T-cell zone reticular cells in the extrafollicular space. We also identified podoplanin-positive epithelial cells as a potential plasma cell (PC) niche. We found two levels of FRC-associated diversity: i) tissue-specific subsets; ii) shared subsets with tissue-specific gene signatures. These findings shed new light on the role of FRCs in supporting SLO-specific immune responses.

ORGANISM(S): Homo sapiens

PROVIDER: GSE193449 | GEO | 2023/02/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Fibroblastic reticular cells serve as primary immune checkpoint in visceral adipose tissues and secure peritoneal immunity

Project description:Immune protection of the body cavities depends on the swift activation of innate and adaptive immune responses in non-classical secondary lymphoid organs known as fat-associated lymphoid clusters (FALCs). While it is well-established that fibroblastic reticular cells (FRCs) are an integral component of the immune-stimulating infrastructure of lymph nodes and other classical secondary lymphoid organs, it has remained elusive whether and how FRCs in FALCs contribute to peritoneal immunity. Using FRC-specific gene targeting, we found that FALCs are underpinned by an elaborated FRC network and that initiation of peritoneal immunity was governed through FRC activation via MyD88-dependent innate immunological sensing. FRC-specific ablation of Myd88 expression blocked recruitment of inflammatory monocytes into FALCs and subsequent CD4+ T cell-dependent B-cell activation. Moreover, containment of Salmonella infection was compromised in conditionally Myd88-deficient mice indicating that FRCs in FALCs function as initial checkpoint in the orchestration of protective immune responses in the peritoneal cavity.

2018-06-12 | E-MTAB-6886 | biostudies-arrayexpress

Fibroblastic reticular cell lineage convergence in Peyer’s patches governs intestinal homeostasis

Project description:Peyer`s patches (PP) are underpinned by a dense network of FRCs. To elaborate the subset composition and topological organization of PP FRCs, we employed well-characterized Ccl19-Cre and Col6a1-Cre mouse models that permit FRC targeting in secondary lymphoid organs. To define PP FRC subsets and their relation to the observed FRC lineages, we isolated fibroblasts from Col6a1Eyfp and Ccl19Eyfp PPs and performed droplet-based single cell transcriptomics analysis. Taken together, the molecular definition of the PP FRC landscape reveals two FRC lineages furnishing distinct microenvironmental niches.

2021-01-22 | E-MTAB-9162 | biostudies-arrayexpress

Single cell RNAseq of immune and stromal cells from human palatine tonsils

Project description:Palatine tonsils are secondary lymphoid organs that are strategically positioned in the oropharynx to secure a first line of defense against oral pathogens. Specialized immune-interacting fibroblasts, generally termed fibroblastic reticular cells (FRC), underpin distinct microenvironments within lymphoid organs to compartmentalize and direct the efficient interaction and activation of immune cells. As a particular anatomical property, palatine tonsils harbor a reticular-shaped lymphoepithelium that generates an antigen sampling zone in the crypts. While the histological ultrastructure and the immune cell composition of human palatine tonsils has been elaborated in detail, the molecular identity of the diverse stromal cell compartments including FRC and the specialized lymphoepithelium remains largely unknown. Here, we have employed single cell transcriptomics and extensive flow cytometric analyses to unveil the molecular identity of tonsillar cells and to disentangle the heterogeneity of fibroblast and epithelial cell subsets in palatine tonsils. Our results reveal a remarkable conservation of stromal cell organization and molecularly-defined subsets in infant and adult human palatine tonsils.

2023-03-30 | E-MTAB-11715 | biostudies-arrayexpress

Activation of TLR9 signaling suppresses the immuno modulating functions of CD55lo fibroblastic reticular cells during bacterial peritonitis

Project description:Fibroblastic reticular cells (FRCs) are heterogeneous. We use single cell RNA sequencing to identify subsets of FRCs in fat-associated lymphoid clusters (FALC) in the mesenteric adipose tissue

2024-04-18 | GSE250571 | GEO

Splenic fibroblastic reticular cells regulate dendritic cell maturation and T-DC interactions required for antiviral immunity

Project description:Stromal cells construct the architecture of the spleen and provide crucial signals that influence the homeostasis and migration of immune cells in the steady state. Fibroblastic Reticular Cells (FRCs) respond to infection via the regulation of many key structural and functional components. Yet, how spleen FRCs contribute to the induction and maintenance of antiviral T cell responses is still poorly defined. We found that ablation of splenic FRCs impacted the generation of virus-specific CD8 T cell during lymphocytic choriomeningitis virus (LCMV) infection in mice. Imaging revealed that during T cell priming in the presence of FRCs, CD8 T cells clustered in the T cell zone with type 1 conventional dendritic cells (cDC1) before moving to the marginal zone to interact with virus-infected cells. In the absence of FRCs, T cells instead clustered with virus-infected cells and cDC1s in the marginal zone, undergoing suboptimal priming due to reduced TCR signalling and unstable DC-T cell interactions. We found that FRCs regulated the early inflammatory wave required for optimal DC activation in vivo. The absence of FRCs thus resulted in diminished DC activation and impaired capacity to prime T cell responses. We further revealed that the presence of an intact FRC network was crucial for the generation of functional effector T cells. Importantly, these early cellular events orchestrated by FRCs also regulated the generation of protective memory T cells upon resolution of infection. Altogether, our study reveals important roles for FRCs for induction of antiviral T cell responses through support for DC maturation, effector CTL generation and the formation of protective memory T cells.

2024-08-16 | GSE274926 | GEO

Single cell RNAseq analysis of fibroblastic reticular cells from murine brachial lymph nodes during inflamed and resting states

Project description:The lymph node is home to resident macrophage populations that are essential for healthy immune function and homeostasis. They are involved in multiple processes including the initiation of the local response to pathogens, halting viral and bacterial spread, and clearance of apoptotic cells, but the macrophage niche and factors that create it are largely undefined. Here we analyse fibroblastic reticular cells (FRCs) as an essential component of the lymph node macrophage niche using single-cell RNA-sequencing. Our analysis revealed that most reticular cell subsets within lymph nodes expressed master macrophage regulator CSF1. We further show that signalling through CSF1R was sufficient to support macrophage development, while in the presence of LPS, FRCs underwent a mechanistic switch and maintained support through CSF1R-independent mechanisms. Our data reveal a critically important role for FRCs in the creation of the parenchymal macrophage niche within LNs.

2023-05-01 | E-MTAB-10908 | biostudies-arrayexpress

Aldh1a2+ fibroblastic reticular cells regulate lymphocyte recruitment in omental milky spots

Project description:Milky spots, lymphoid clusters present in visceral adipose tissue omentum, play central roles in the regulation of abdominal immunity. Milky spots exhibit hybrid nature between secondary lymph organs and ectopic lymphoid tissues, yet the mechanism of their development and maturation is poorly understood. Here, we identified a subset of fibroblastic reticular cells (FRCs) that are uniquely present in omental milky spots. These FRCs were characterized by the expression of retinoic acid converting enzyme, Aldh1a2, and endothelial cell marker, Tie2, in addition to canonical FRC-associated genes. Diphtheria toxin-mediated ablation of Aldh1a2+ FRCs resulted in the alteration in milky spot structure with a significant reduction in size and cellularity. Mechanistically, Aldh1a2+ FRCs regulated the display of chemokine CXCL12 on high endothelial venules (HEVs), which recruit blood-borne lymphocytes from circulation. We further found that Aldh1a2+ FRCs are required for the maintenance of peritoneal lymphocyte composition. These results illustrate the homeostatic roles of FRCs in the formation of non-classical lymphoid tissues.

2023-02-14 | GSE224023 | GEO

Aldh1a2+ fibroblastic reticular cells regulate lymphocyte recruitment in omental milky spots (single cell RNA-Seq)

2023-02-14 | GSE224483 | GEO

Aldh1a2+ fibroblastic reticular cells regulate lymphocyte recruitment in omental milky spots (stromal fraction of wild-type)

2023-02-14 | GSE224315 | GEO

Single-cell RNA sequencing of lymph node stromal cells reveals niche-associated heterogeneity

Project description:Stromal cells (SCs) establish the compartmentalization of lymphoid tissues critical to the immune response. However, the full diversity of lymph node (LN) SCs remains undefined. Using droplet-based single-cell RNA sequencing we identified 9 peripheral LNs non-endothelial SC subsets. Included are the established subsets Ccl19hi T-zone reticular cells (TRCs), marginal reticular cells, follicular dendritic cells (FDCs) and perivascular cells. We also identified Ccl19lo TRCs, likely including cholesterol-25-hydroxylase+ cells located at the T-zone perimeter, Cxcl9+ TRCs in the T-zone and interfollicular region, CD34+ SCs in the capsule and medullary vessel adventitia, indolethylamine N-methyltransferase+ SCs in the medullary cords and Nr4a1+ SCs in several niches. These data help define how transcriptionally distinct LN SCs support niche-restricted immune functions and they provide evidence that many SCs are in an activated state.

2018-05-10 | GSE112903 | 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