Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Sequential DC-intrinsic Lymphotoxin Beta Receptor and Retinoic Acid Receptor signals regulate cDC2 fates

ABSTRACT: Type II conventional dendritic cells (cDC2) are functionally and phenotypically heterogenous. Previous work identified two major cDC2 subsets (cDC2A and cDC2B) and a transcriptionally related monocytic DC3 subset; however, the underlying microenvironmental cues governing their distinct differentiation pathways remain unclear. Here we delineate cDC2 lineage relationships, and the sequential signals required for cDC2A specification and maintenance. We show that T-bet+ cDC2A, arising from a Clec9a+ DC progenitor, express the retinol receptor RBPR2, require cell-intrinsic retinoic acid (RA) signaling for their maintenance in the spleen and mesenteric lymph nodes, and depend on intrinsic RA receptor signaling to sustain downstream Notch signals. Prior to their expression of T-bet, splenic cDC require cell-intrinsic Lymphotoxin beta receptor (LTbR) which is needed to reduce F-actin content and prevents the escape of cDC2 to the blood. We propose a novel mechanism whereby splenic cDC2-intrinsic LTbR signaling anchors cDC2 within the spleen so that they may access macromolecules such as retinol to promote cDC2A development.

ORGANISM(S): Mus musculus

PROVIDER: GSE302089 | GEO | 2025/11/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

ADAM10 shapes myeloid antigen-presenting cell homeostasis in the splenic marginal zone

Project description:The spleen contains phenotypically and functionally distinct cDC1 and cDC2 subpopulations, which each can be divided into several smaller and less-well characterized subsets. Despite advances in understanding the complexity of DC ontogeny and function by transcriptional programming, the significance of post-translational modifications in controlling tissue-specific cDC (subset) immunobiology remains elusive. Here, we identified the cell surface-expressed A-disintegrin-and-metalloproteinase 10 (ADAM10) as an essential regulator of cDC1 and cDC2 homeostasis in the splenic marginal zone (MZ). Mice with a CD11c-specific deletion of ADAM10 (ADAM10ΔCD11c) exhibited a complete loss of splenic ESAMhi cDC2A, because ADAM10 controlled their commitment, differentiation, survival, and EBI2-mediated localization within the MZ. Moreover, we discovered that ADAM10 is a molecular switch regulating cDC2 subset heterogeneity in the spleen, as this unbalanced cDC2A homeostasis in the absence of ADAM10 was compensated for by the emergence of a novel Clec12a+ cDC2B subset, closely resembling cDC2 generally found in peripheral lymph nodes. Moreover, in ADAM10ΔCD11c mice terminal differentiation of cDC1 was abrogated, resulting in reduced numbers of Langerin+ cDC1.

2023-06-27 | GSE154309 | GEO

ADAM10 shapes myeloid antigen-presenting cell homeostasis in the splenic marginal zone

2021-09-06 | GSE154767 | GEO

Transcription Factor TLX1 Controls Retinoic Acid Signaling to Ensure Spleen Development [ChIP-Seq]

Project description:The molecular mechanisms that underlie spleen development and congenital asplenia, a condition linked to increased risk of overwhelming infections, remain largely unknown. The transcription factor TLX1 controls cell fate specification and organ expansion during spleen development, and Tlx1 deletion causes asplenia in mice. Deregulation of TLX1 expression has recently been proposed in the pathogenesis of congenital asplenia in patients carrying mutations of the gene-encoding transcription factor SF-1. Herein, we have shown that TLX1-dependent regulation of retinoic acid (RA) metabolism is critical for spleen organogenesis. In a murine model, loss of Tlx1 during formation of the splenic anlage increased RA signaling by regulating several genes involved in RA metabolism. Uncontrolled RA activity resulted in premature differentiation of mesenchymal cells and reduced vasculogenesis of the splenic primordium. Pharmacological inhibition of RA signaling in Tlx1-deficient animals partially rescued the spleen defect. Finally, spleen growth was impaired in mice lacking either cytochrome 26B1 (Cyp26b1), which results in excess RA, or retinol dehydrogenase 10 (Rdh10), which results in RA deficiency. Together, these findings establish TLX1 as a critical regulator of RA metabolism and provide mechanistic insight into the molecular determinants of human congenital asplenia.

2016-07-01 | GSE81660 | GEO

Transcription Factor TLX1 Controls Retinoic Acid Signaling to Ensure Spleen Development [ChIP-Seq]

2016-07-01 | E-GEOD-81660 | biostudies-arrayexpress

Transcription Factor TLX1 Controls Retinoic Acid Signaling to Ensure Spleen Development [Microarray Expression]

Project description:The molecular mechanisms underlying asplenia, a condition often associated with overwhelming infections remain largely unknown. During spleen development, the transcription factor TLX1 controls morphogenesis and organ expansion, and loss of it causes spleen agenesis. However, the downstream signaling pathways that are deregulated in the absence of TLX1 are mostly unknown. Herein, we demonstrate that loss of Tlx1 in the splenic mesenchyme causes increased retinoic acid (RA) signaling. Increased RA activity causes premature differentiation of the splenic mesenchyme and reduced vasculogenesis of the splenic anlage. Moreover, excess or deficiency in RA signaling, as observed in Cyp26b1 or Rdh10 mutants respectively, also results in spleen growth arrest. Genome-wide analysis revealed that TLX1 binds RA-associated genes through the AP-1 site and cooperates with the AP-1 family transcription factors to regulate transcription. Pharmacological inhibition of RA signaling partially rescues the spleen defect. These findings establish the critical role of TLX1 in controlling RA metabolism, and provide novel mechanistic insights into the molecular determinants underlying congenital asplenia.

2016-07-01 | GSE68519 | GEO

Transcription Factor TLX1 Controls Retinoic Acid Signaling to Ensure Spleen Development [Microarray Expression]

2016-07-01 | E-GEOD-68519 | biostudies-arrayexpress

Transcriptome profiling of spleen and duodenum upon lymphotoxin beta receptor (LTbR) induction

Project description:To study the effect of LTbR induction on spleen and duodenum transcriptome, we performed RNA sequencing of the spleen and intestine after Intravenous LTbR agonist AC H6 or isotype treatment. We analyzed differential gene expression.

2019-12-31 | GSE126115 | GEO

Genome-wide analysis of gene expression in mouse spleen stroma

Project description:Comparison between gene expression profiles of splenic stroma from wild type and lymphotoxin beta receptor knockout mice. The goal was to identify a set of genes which expression in splenic stroma is under lymphotoxin control and which can potentially be important for proper stroma development and function in secondary lymphoid organs. Total RNA isolated from mechanically separated stroma and splenocytes of wild type and LTbR-KO mice, as well as cultured spleen stroma cells from wild type mice. technical replicate - extract: A,B technical replicate - extract: C,D technical replicate - extract: E,F technical replicate - extract: G,H

2013-11-13 | E-GEOD-52294 | biostudies-arrayexpress

Vitamin A nutritional status and retinoic acid as regulators of gene expression in rat liver

Project description:Vitamin A (retinol) is an essential precursor for the production of retinoic acid (RA), which in turn is a major regulator of gene expression, affecting cell differentiation throughout the body. Understanding how vitamin A nutritional status, as well as therapeutic retinoid treatment, regulates the expression of retinoid homeostatic genes is important for improving dietary recommendations and therapeutic strategies using retinoids. This study investigated genes central to processes of retinoid uptake and storage, release to plasma, and oxidation in the liver of rats under steady-state conditions after different exposures to dietary vitamin A (deficient, marginal, adequate and supplemented), and acutely after administration of a therapeutic dose of all-trans-RA. Over a very wide range of dietary vitamin A, lecithin:retinol acyltransferase (LRAT) as well as multiple cytochrome P450s (CYP26A1, CYP26B1, and CYP2C22) differed by diet and were highly correlated with one another and with vitamin A status assessed by liver retinol concentration (all correlations, P<0.05). After acute treatment with RA, the same genes were rapidly and concomitantly induced, preceding RARß, a classical direct target of RA. CYP26A1 mRNA exhibited the greatest dynamic range (change of log26 in 3 h). Moreover, CYP26A1 increased more rapidly in the liver of RA-primed rats than naïve rats. By in situ hybridization, CYP26A1 mRNA was strongly regulated within hepatocytes, closely resembling RBP4 in location. Overall, whether RA is produced endogenously from retinol or administered exogenously, changes in retinoid homeostatic gene expression simultaneously favor both retinol esterification and RA oxidation, with CYP26A1 exhibiting the greatest dynamic change.

2011-09-01 | GSE24104 | GEO

Decellularized splenic matrix as a scaffold for spleen bioengineering

Project description:The spleen is considered a non-essential organ. However, its importance is increasingly clear, given the serious disorders caused by its absence or dysfunction, e.g., greater susceptibility to infections, thromboembolism and cancer. Also, non-functionality of the spleen can lead to higher risk of infection and death in patients with serious diseases, such as HIV, myeloma, and leukemia. Surgical techniques to preserve the spleen and maintain splenic function have become increasingly common. However, the morbidity and mortality associated with its absence and dysfunction are still high. We used the decellularization technique to obtain a viable splenic scaffold for recellularization in vitro and propose the idea of bioengineered spleen transplantation to the host. In our study, we demonstrated that the scaffold created after decellularization presents good removal of residual DNA and SDS, which are essential to prevent immunogenic responses and transplantation failure. Also, the main components of the splenic matrix, such as collagens, glycoproteins, and proteoglycans, were preserved. We observed the maintenance of important structural components such as white pulp, marginal zone and red pulp, in addition to the network of vascular ducts. The scaffold we developed was subsequently recellularized with stromal cells from the spleen of neonatal rats, demonstrating adhesion, proliferation and viability of cells in contact with the scaffold. Therefore, the splenic scaffold is very promising for use in studies on spleen reconstruction and transplantation, with the aim of complete recovery of splenic function.

2021-07-15 | PXD020363 | JPOST Repository

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