Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptional and functional profiling defines human small intestinal macrophage subsets

ABSTRACT: Macrophages (Mf) are instrumental in maintaining immune homeostasis in the intestine, yet studies on origin and heterogeneity of human intestinal Mf are scarce. Here, we identified four distinct Mf subpopulations in human small intestine (SI). Assessment of their turnover in duodenal transplants revealed that all Mf subsets were completely replaced over time; Mf1 and Mf2, phenotypically similar to peripheral blood monocytes (PBMo), were largely replaced within 3 weeks, whereas two subsets with features of mature Mf, Mf3 and Mf4, exhibited significantly slower replacement. Mf3 and Mf4 localized differently in SI; Mf3 formed a dense network in mucosal lamina propria, whereas Mf4 was enriched in submucosa. Transcriptomic analysis showed that all Mf subpopulations subsets were markedly distinct from PBMo and dendritic cells (DC). Compared to PBMo, Mf subpopulations showed reduced responsiveness to proinflammatory stimuli, but were proficient at endocytosis of particulate and soluble material. These data provide a comprehensive analysis of human SI Mf population and suggest a precursor-progeny relationship with PBMo.

PROVIDER: EGAS00001002093 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Json Xml

Similar Datasets

Human intestinal DC and MNP

Project description:Parallel subpopulations of CD11c+ MNPs present in the mouse intestine similarly exist in the human intestine (Fig. 6A and Ref. (Merad et al., 2013)). To evaluate whether these distinct subpopulations of MNPs from human intestinal tissue functioned similarly, we examined the phenotypic properties of CD103+ DCs and CD14+ MNPs (which express CX3CR1 (Kamada et al., 2008)) within the CD11c+ MHCII+ fraction of LPMCs (Fig. 6B). In contrast to CD103+ DCs, CD14+ MNPs expressed CD64 as well as higher levels of CD86. Consistent with the phenotypic characterization of these subsets, transcriptional analysis of these populations by RNA-seq revealed higher levels of CLEC9A, XCR1, and CD207 expression in the CD103+ cells, while MERTK, STAB1, and CX3CR1 were higher in the CD14+ cells (Fig. 6C). We tested the potential of these subsets to induce IL-22 production by co-culturing TLR-stimulated CD14+ MNPs and CD103+ DCs from human intestinal resections with intestinal ILCs. Intracellular cytokine staining at 18 hours revealed that the CD14+ MNP were more effective than the CD103+ DCs at stimulating IL-22 production by ILCs (Fig. 6D). Neither cell population induced significant IL-17 or IFNg production by ILCs (Fig. 6D, 6E).

2014-07-15 | GSE59386 | GEO

Human intestinal T cell and paired blood transcriptomes

Project description:The intestinal mucosa harbors the largest accumulation of T lymphocytes in the body. While these T cells play an important role in immune homeostasis, they are also implicated in triggering and maintaining pathological intestinal inflammation. In humans they are poorly characterised, and even mouse transcriptomes have been reported for only a few individual cell types, many of which lack direct human equivalents. Using expression microarrays on T cells isolated from ileal biopsies and in silico analysis, we present here an unbiased, transcriptome-wide view of function in T cell subpopulations of the healthy human intestine and delineate signalling pathways that are distinct from those seen in peripheral blood T cells. Paired blood and intestinal biopsies from 6 age/sex matched healthy human subjects. Intestinal biopsies processed to release intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL). All samples then used to generate T effector memory (Tem) cells of CD4+ and CD8+ subsets by flow sorting. 6 individuals; 3 cell sources per individual (blood, LPL, IEL); 2 Tem subsets per cell source (CD4+ and CD8+). 36 arrays in total

2014-05-06 | E-GEOD-49877 | biostudies-arrayexpress

Human blood CD1c⁺ dendritic cells encompass CD5-high and CD5-low subsets that differ significantly in phenotype, gene expression and functions

Project description:There are three major dendritic cell (DC) subsets in both human and mouse, plasmacytoid DCs (pDCs) and two types of conventional DCs (cDCs), cDC1s and cDC2s. cDC2s are important for polarizing CD4+ naive T cells into different subsets including Th1, Th2, Th17, Th22 and regulatory T cells (Tregs). In mice, cDC2s can be further divided into phenotypically and functionally distinct subgroups. However, subsets of human cDC2s have not been reported. In the present study, we showed that human blood CD1c+ conventional DCs (cDC2s) can be further separated into two subpopulations according to their CD5 expression status. Comparative transcriptome analyses showed that the CD5high DCs expressed higher levels of cDC2-specific genes, including IRF4, which is essential for the cDC2 development and its migration to lymph nodes. In contrast, CD5low DCs preferentially expressed monocyte-related genes, including the lineage-specific transcription factor MAFB. Furthermore, compared with CD5low subpopulation, CD5high subpopulation showed stronger migration toward CCL21 and overrepresentation among migratory DCs in lymph nodes. Additionally, the CD5high DCs induced naïve T-cell proliferation more potently than the CD5low DCs. Moreover, CD5high DCs induced higher levels of IL-10-, IL-22- and IL-4-producing T-cell formation, whereas CD5low DCs induced higher levels of IFN-γ-producing T-cell formation. Thus, we show that human blood CD1c+ cDC2s encompass two subsets that differ significantly in phenotype, gene expression, and functions. We propose that these two subsets of human cDC2s could potentially play contrasting roles in immunity or tolerance.

2017-03-07 | GSE77649 | GEO

Distinct human stem cell populations in small and large intestine

Project description:The intestine is composed of an epithelial layer, containing rapidly proliferating cells that mature into two distinct anatomic regions, the small and the large intestine. Although previous studies have identified stem cells as the cell-of-origin for the whole intestine, no studies have compared stem cells derived from the small and large intestine. Here, we report intrinsic differences between these two populations of cells. Primary epithelial cells isolated from human fetal small and large intestine and expanded with Wnt agonist, R-spondin 2, displayed differential expression of stem cell markers and separate hierarchical clustering of gene expression involved in differentiation, proliferation and disease pathways. Using a three-dimensional in vitro differentiation assay, single cells derived from small and large intestine formed distinct organoid architecture with cellular hierarchy similar to that found in primary tissue. Our characterization of human fetal intestinal stem cells defies the classical definition proposed by most where small and large intestine are repopulated by an identical epithelial stem cell and raises the question of the importance of intrinsic and extrinsic cues in the development of intestinal diseases. 12 samples were analyzed. They consisted of human fetal small and large intestine (SI; n=6 and LI; n=6) stem cells, expanded with Wnt agonist and R-spondin 2. Differential expression of genes in epithelial cells from both the large and small intestine were observed.

2015-01-15 | E-GEOD-56525 | biostudies-arrayexpress

Resident memory CD8 T cells persist for years in human small intestine

Project description:Resident memory CD8 T cells (Trm) have been shown to provide effective protective responses in the small intestine (SI) in mice. A better understanding of the generation and persistence of SI CD8 Trm cells in humans may have implications for intestinal immune-mediated diseases and vaccine development. Analyzing normal and transplanted human SI we demonstrated that the majority of SI CD8 T cells were bona fide CD8 Trm cells that survived for over 1 year in the graft. Intraepithelial and lamina propria CD8 Trm cells showed a high clonal overlap and a repertoire dominated by expanded clones, conserved both spatially in the intestine and over time. Functionally, lamina propria CD8 Trm cells were potent cytokine-producers, exhibiting a polyfunctional (IFN-γ+ IL-2+ TNF-α+) profile, and efficiently expressed cytotoxic mediators after stimulation. These results suggest that SI CD8 Trm cells could be relevant targets for future oral vaccines and therapeutic strategies for gut disorders.

| EGAS00001003676 | EGA

Gene expression profiling of small intestine (SI) NKp46+RORgt+ and NKp46+RORgt- Innate Lymphoid Cells (ILCs)

Project description:The aim of this study was to analyze the global transcriptional profiles of small intestine (SI) Innate Lymphoid Cells (ILCs) expressing the NK cell marker NKp46. Based on differential expression of the RORgt transcription factor SI NKp46+ ILCs can be divided in NKp46+RORgt- and NKp46+RORgt+ cells. While NKp46+RORgt- cells produce IFN-g, like conventional Natural Killer (NK) cells, NKp46+RORgt+ cells secrete IL-22, like Lymphoid Tissue inducer (LTi) cells. We compared the global transcriptional profiles of both NKp46+RORgt- and NKp46+RORgt+ cells to conventional splenic NK cells and to SI NKp46-RORgt+ cells, which contain adult LTi cells. By following this approach, we showed that SI NKp46+RORγt- ILCs correspond to SI NK cells. We also identified a transcriptional program conserved in adult SI NKp46+RORγt+, NKp46-RORγt+ ILCs and fetal LTi. The various ILC cell populations analyzed in this study were isolated from C57BL/6 RORc(gt)+/GFP reporter mice. SI NKp46+RORγt- (NKp46+GFP-) cells, SI NKp46+RORγt+ cells (NKp46+GFPlow and NKp46+GFPhigh cells) and NKp46-RORγt+ ILCs, including adult LTi cells , were sorted by flow cytometry from CD3- lamina propria cells of small intestine (SI) of RORc(γt)+/GFP reporter mice . Splenic NKp46+RORγt- (NKp46+GFP-) cells were also sorted as the reference for conventional NK cells. Two replicates of each populations were produced and analyzed.

2011-06-20 | E-GEOD-29777 | biostudies-arrayexpress

Expression profiles of human NK cell subsets

Project description:It is known that natural killer (NK) cells are a heterogeneous population of functionally distinct NK cell subsets. Here we report on different genomic, phenotypic and functional properties of human NK cell subsets derived from peripheral blood, thymus and bone marrow. NK cell subpopulations were defined via expression of CD56 and CD16.

2017-01-01 | GSE57479 | GEO

Proteomic analysis reveals a protective role of specific macrophage subsets in liver repair

Project description:Macrophages are a heterogeneous population of immune cells that play central roles in a broad range of biological processes, including the resolution of inflammation. Although diverse macrophage subpopulations have been identified, the characterization and functional specialization of certain macrophage subsets in inflamed tissues remain unclear. Here we uncovered a key role of specific macrophage subsets in tissue repair using proteomics, bioinformatics and functional analyses. We isolated two hepatic monocyte-derived macrophage subpopulations: Ly6ChiCX3CR1lo macrophages and Ly6CloCX3CR1hi macrophages during distinct phases of acute liver injury and employed label-free proteomics approach to profile the proteome of these cells. We found that the wound healing- and endocytosis-related proteins were specifically enriched in Ly6CloCX3CR1hi macrophages. Intriguingly, 12/15-lipoxygenase (Alox15), the most strongly up-regulated protein in Ly6CloCX3CR1hi macrophages, was identified as a specific marker for these macrophages. In co-culture systems, Ly6CloCX3CR1hi macrophages specifically induced hepatocyte proliferation. Furthermore, selective depletion of this population in CD11b-diphtheria toxin receptor mice significantly delayed liver repair. Overall, our studies shed light on the functional specialization of distinct macrophage subsets in the resolution of inflammation.

2019-10-08 | PXD011958 | Pride

Engineering transplantable jejunal mucosal grafts using primary patient-derived organoids for children with intestinal failure

Project description:Intestinal failure (IF), following extensive anatomical or functional loss of small intestine (SI), hasdebilitating long-term consequences on children1. Priority of care is to increase the child’s length of functional intestine, jejunum in particular, to promote nutritional independence2. Here we construct autologous jejunal mucosal grafts using primary patient biomaterials. We show that organoids derived from patients can be expanded efficiently in vitro. In parallel, we generate decellularized human intestinal matrix with intact nanotopography, which form optimal biological scaffolds. Remarkably, proteomic and Raman spectroscopy analyses reveal highly analogous biochemical profiles of human SI and colon scaffolds, indicating that both can be used interchangeably as platforms for intestinal engineering. Indeed, seeding jejunal organoids onto either scaffold type reliably reconstructs grafts that exhibit several aspects of physiological jejunal function with potential to survive after transplantation. Our findings provide proof-of-concept data for engineering IF patient-specific jejunal grafts, ultimately aiding in restoration of nutritional autonomy.

2020-09-16 | PXD019816 | Pride

Gene expression profiling of small intestine (SI) NKp46+RORgt+ and NKp46+RORgt- Innate Lymphoid Cells (ILCs)

2011-06-20 | GSE29777 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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