Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Human intestinal stromal cells promote homeostasis in normal mucosa but inflammation in Crohn's disease in a retinoic acid-deficient manner

ABSTRACT: Stromal cell (SC) contributions to intestinal inflammation are inadequately understood. Here we show that CD90+vimentin+SMA- SCs isolated from Crohn’s disease intestine (Crohn’s SCs) displayed higher levels of spontaneously released and microbiota-induced inflammatory mediators, including IL-6 and TGF-b, and surface adhesion molecules, than SCs isolated from healthy intestine (Normal SCs). Comparative transcriptome analysis confirmed the predominance of upregulated inflammatory response and cytokine signaling genes and pathway molecules in Crohn’s SCs. Importantly, intestinal SCs provided retinoic acid (RA), which regulated DC maturation, and in an in vitro cross-talk system E. coli LF82-stimulated Crohn’s SCs promoted differentiation of more inflammatory TNFhi/IL-12lo/RAlo DCs and IFN-ghi/IL-17hi effector T cells than Normal SCs. Explaining this finding, Crohn’s SCs synthesized less RA and expressed more retinaldehyde reductase DHRS3, which inhibits retinol conversion to retinal, than Normal SCs. Our findings uncover microbe-SC crosstalk in which mucosal SCs initiate and perpetuate DC-driven T-cell-mediated inflammation in Crohn’s disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE178994 | GEO | 2024/07/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Schwann cell plasticity regulates neuroblastic tumor cell differentiation - phosphoproteomics

Project description:The remarkable plasticity of Schwann cells (SCs) is essential for nerve regeneration but also contributes to neuropathies and cancer progression. It has not yet been investigated whether the adaptive potential of SCs is manifested in stromal, tumor associated SCs characteristically found within a benign subtype of neuroblastic tumors (NBTs). We here performed transcriptome profiling of human NBTs, rich and poor in SC stroma, as well as human injured nerves, rich in repair SCs, revealing that stromal SCs exhibit a repair SC characteristic gene expression signature. In turn, primary repair SCs had a pro-differentiating and anti-proliferative effect on NBT cell lines after direct and trans-well co-culture. Within the pool of secreted stromal/repair SC factors, we identified EGFL8, a matricellular protein with so far undescribed function, to induce neuronal differentiation of aggressive NBT cells. EGFL8 expression further correlated with favorable tumor stage and increased patient survival. Our findings suggest that stromal SCs exert nerve repair associated functions in the tumor-environment and underline the therapeutic value of SC-derived factors for aggressive, SC stroma-poor NBTs.

2021-01-04 | PXD022217 | Pride

Schwann cell plasticity regulates neuroblastic tumor cell differentiation

2021-01-13 | PXD018267 | Pride

Mouse Muscle Stem Cell Proteome during Activation and CPEB1 Dependent Proteome in Mouse Muscle Stem Cell

Project description:Muscle Stem Cells or satellite cells (SCs) are required for muscle regeneration. In resting muscles, SCs are kept in quiescence. After injury, SCs undergo rapid activation, proliferation and differentiation to repair damaged muscles. The transcriptome alteration during SC activation is well characterized. While transcriptome is not exactly represent proteome because of post-transcriptional regulations such as miRNA induced gene silencing. However, little is known about SC proteome. We obtained quisecent SCs (QSCs) and freshly isolated SCs (fiSCs, early activated SCs) and activated SCs (ASCs) for high resolution mass spectrometry Bruker timsTOF Pro. Thus, we uncovered the QSC proteome. By comparison of QSC proteome to fiuSCs proteome or ASCs proteome, we identified the pathways that are differentially expressed between them. Forthermore, we characterized a translational regulator CPEB1 reprogrammed translation landscape for SC activation.

2021-11-05 | PXD018865 | Pride

The biological and molecular heterogeneity of breast cancers correlate with their cancer stem cell content

Project description:Pathways that govern normal stem cell (SC) function are often subverted in cancer. Here, we report the isolation to near purity of human normal mammary SC (hNMSCs), from cultured mammospheres, based on their ability to retain the lipophilic dye PKH26 as a consequence of their quiescent nature. We demonstrated that PKH26-positive cells possess all the characteristics of hNMSCs. The transcriptional profile of PKH26-positive cells (hNMSC signature) was able to predict biological and molecular features of breast cancers. By using markers of the hNMSC signature, we could prospectively isolate SCs from the normal gland and from breast tumors. Poorly-differentiated aggressive (G3) cancers displayed higher content of prospectively isolated cancer SCs, than well-differentiated less aggressive (G1) cancers. By comparing G3 and G1 tumors in xenotransplantation experiments, we directly demonstrated that G3s are enriched in cancer SCs. Our data support the notion that the heterogeneous phenotypical and molecular traits of human breast cancers are a function of their SC content.

2009-11-07 | GSE18931 | GEO

3 days injured in vivo ASCs proteome

Project description:Muscle Stem Cells or satellite cells (SCs) are required for muscle regeneration. In resting muscles, SCs are kept in quiescence. After injury, SCs undergo rapid activation, proliferation and differentiation to repair damaged muscles. The transcriptome alteration during SC activation is well characterized. While transcriptome is not exactly represent proteome because of post-transcriptional regulations such as miRNA induced gene silencing. However, little is known about SC proteome. We obtained in vivo activated SCs (ASCs) from 3 days post injured muscles for high resolution mass spectrometry Bruker timsTOF Pro. Compared with QSC proteome,, we identified the pathways that are differentially expressed between them.

2021-11-04 | PXD023656 | Pride

A circadian clock is essential for homeostasis of group 3 innate lymphoid cells in the gut

Project description:Interleukin (IL)-2 is a pleiotropic cytokine that is necessary to prevent chronic inflammation in the gastrointestinal tract. The protective effects of IL-2 involve the generation, maintenance and function of regulatory T cells (Tregs), and low-dose IL-2 has emerged as a potential therapeutic strategy in inflammatory bowel disease (IBD) patients. However, the cellular and molecular pathways that control the production of IL-2 in the context of intestinal health are undefined. Here we identify that IL-2 is acutely required to maintain Tregs and immunologic homeostasis throughout the gastrointestinal tract. Strikingly, lineage-specific deletion of IL-2 in T cells could recapitulate these phenotypes in the large intestine, but not in the small intestine. Unbiased analyses revealed that group 3 innate lymphoid cells (ILC3) are the dominant cellular source of IL-2 in the small intestine, which is selectively induced by IL-1β. Macrophages produce IL-1β in the small intestine and activation of this pathway involves MyD88- and Nod2-dependent sensing of the microbiota. Loss-of-function studies defined that ILC3-derived IL-2 is essential to maintain Tregs, immunologic homeostasis and oral tolerance to dietary antigens uniquely in the small intestine. Furthermore, ILC3 production of IL-2 was significantly reduced in the small intestine of Crohn’s disease patients, and this correlated with diminished Tregs. Collectively, these results reveal a previously unappreciated pathway whereby a microbiota- and IL-1β-dependent axis promotes ILC3 production of IL-2 to orchestrate immune regulation in the small intestine.

2019-08-28 | GSE136567 | GEO

Innate lymphoid cells support regulatory T cells in the intestine through interleukin-2

2019-03-31 | GSE126580 | GEO

The biological and molecular heterogeneity of breast cancers correlate with their cancer stem cell content

2009-11-06 | E-GEOD-18931 | biostudies-arrayexpress

Schwann cell plasticity regulates neuroblastic tumor cell differentiation

2020-12-23 | GSE147635 | GEO

miR-146 connects stem cell identity with metabolism and pharmacological resistance in breast cancer

Project description:Although ectopic overexpression of miRNAs can influence mammary normal and cancer stem cells (SCs/CSCs), their physiological relevance remains uncertain. Here, we found that the miR-146 family is linked to SC identity, since: i) their expression is very high in SCs/CSCs from human/mouse primary mammary tissues; correlates with the basal-like breast cancer subtype, which typically has a high CSC content; and specifically distinguishes cells with SC/CSC identity; ii) miR-146 depletion reduces SC/CSC self-renewal in vitro and the number of tumor-initiating cells in vivo. Analysis of the transcriptional effects of miR-146 in breast SC-like cells revealed a complex network of highly connected miR-146 targets related to quiescence, transcription and metabolic pathways (one-carbon pool, purine synthesis and folate metabolism). As predicted by our analysis, SCs/CSCs display innate resistance to anti-folate therapy that can be reversed by miR-146 depletion, unmasking a “hidden vulnerability” that could be exploited for the development of anti-CSC therapies.

2020-01-21 | GSE131876 | 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