Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Deficiency in peroxisomes underlies failures in neonatal hepatic immune cell hematopoiesis and antigen presentation in a severe Zellweger disease model

ABSTRACT: Peroxisome Biogenesis disorders (PBDs) represent a group of metabolic conditions that cause severe developmental defects. Peroxisomes are essential metabolic organelles, present in virtually every eukaryotic cell and mediating key processes in immunometabolism. To date, the full spectrum of PBDs remains to be identified, and the impact PBDs have on immune function is unexplored. This study presents a characterization of the hepatic immune compartment of a neonatal PBD mouse model at single-cell resolution to establish the importance and function of peroxisomes in developmental hematopoiesis. We report that hematopoietic defects are a feature in a severe PBD murine model. Finally, we identify a role for peroxisomes in the regulation of the major histocompatibility class II expression and antigen presentation to CD4+ T cells in dendritic cells. This study adds to our understanding of the mechanisms of PBDs and expands our knowledge of the role of peroxisomes in immunometabolism.

ORGANISM(S): Mus musculus

PROVIDER: GSE248598 | GEO | 2024/05/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Deficiency in peroxisomes underlies failures in neonatal hepatic immune cell hematopoiesis and antigen presentation in a severe Zellweger disease model

Project description:Deficiency in peroxisomes underlies failures in neonatal hepatic immune cell hematopoiesis and antigen presentation in a severe Zellweger disease model

| PRJNA1044828 | ENA

Gene expression profiles of fibroblasts and induced pluripotent stem cells (iPSCs) from individuals with Zellweger spectrum disorder (ZSD), a class of peroxisome biogenesis disorder, and healthy controls

2015-03-24 | GSE43996 | GEO

DNA methylation profiles of fibroblasts and induced pluripotent stem cells (iPSCs) from individuals with Zellweger spectrum disorder (ZSD), a class of peroxisome biogenesis disorder, and healthy controls

2015-05-19 | GSE68134 | GEO

A Drosophila model for the Zellweger spectrum of peroxisome biogenesis disorders

Project description:Human peroxisome biogenesis disorders are lethal genetic disease in which abnormal peroxisome assembly compromises overall peroxisome and cellular function. Peroxisomes are ubiquitous membrane-bound organelles involved in several important biochemical processes, notably lipid metabolism and the use of reactive oxygen species for detoxification. Using cultured cells, we systematically characterized the peroxisome assembly phenotypes associated with dsRNA-mediated knockdown of 14 predicted Drosophila homologs of PEX genes (encoding peroxins; required for peroxisome assembly and linked to peroxisome biogenesis disorders), and confirmed that at least 13 of them are required for normal peroxisome assembly. We also demonstrate the relevance of Drosophila as a genetic model for the early developmental defects associated with the human peroxisome biogenesis disorders. Mutation of the PEX1 gene is the most common cause of peroxisome biogenesis disorders and is one of the causes of the most severe form of the disease, Zellweger syndrome. Inherited mutations in Drosophila Pex1 correlate with reproducible defects during early development. Notably, Pex1 mutant larvae exhibit abnormalities that are analogous to those exhibited by Zellweger syndrome patients, including developmental delay, poor feeding, severe structural abnormalities in the peripheral and central nervous systems, and early death. Finally, microarray analysis defined clusters of genes whose expression varied significantly between wild-type and mutant larvae, implicating peroxisomal function in neuronal development, innate immunity, lipid and protein metabolism, gamete formation, and meiosis. Expression profiles were analyzed in triplicate from whole larvae of wild-type and pex1 homozygous mutant Drosophila.

2011-07-02 | E-GEOD-30362 | biostudies-arrayexpress

Peroxisomes are dispensable for normal renal function.

Project description:Peroxisomes are highly abundant in proximal tubules where peroxisomal enzymes have been proposed to play an important role in a variety of metabolic and antioxidant functions. This hypothesis was supported by human genetic studies that identified mutations leading to peroxisomal biogenesis deficiency, resulting in severe multi-organ damage (Zellweger’s spectrum disorders (ZSD)), including renal impairment. However, the role of proximal tubule peroxisomes in renal (patho)physiology remains uninvestigated. We addressed this question in mice with conditional ablation of peroxisomal biogenesis in the renal tubule. Our results demonstrate that renal tubular peroxisomes are dispensable for normal renal function and suggest that renal damage in ZSD patients is of extrarenal origin.

2022-03-02 | GSE179202 | GEO

Project description:Zellweger spectrum disorder (PBD-ZSD) is a disease continuum caused by mutations in a subset of PEX genes required for normal peroxisome assembly and function. Their clinical manifestations highlight the importance of peroxisomes in the development and functions of the central nervous system, liver, and other organs. Although much is known about peroxisome assembly and activities, the underlying bases for the cell-type specificity of disease are not fully elucidated. We reprogrammed skin fibroblasts from PBD-ZSD patients into induced pluripotent stem cells (iPSCs) and report their DNA methylation profiles as well as those of matching healthy controls. Dermal fibroblast cultures from 6 PBD-ZSD patient and 3 healthy control donors were reprogrammed into iPSCs by transfection with retroviruses designed to express the human OCT4, SOX2, KLF4 and c-MYC genes. Fibroblasts and iPSCs were cultured in 1:1 ratio of DMEM:F12 medium supplemented with 20% KSR at 37°C with 5% CO2 until confluence for RNA extraction. The overall goal was to confirm the epigenetic reprogramming of iPSCs and identify loci that are differentially methylated between PBD-ZSD patient and healthy control cells in order to gain insights into the pathomechanisms of disease.

2015-05-19 | E-GEOD-68134 | biostudies-arrayexpress

A Drosophila model for the Zellweger spectrum of peroxisome biogenesis disorders

2011-07-02 | GSE30362 | GEO

The biochemical basis of mitochondrial dysfunction in Zellweger Spectrum Disorder

Project description:Peroxisomal Biogenesis Disorders (PBDs) are genetic disorders of peroxisome biogenesis and metabolism that are characterized by profound developmental and neurological phenotypes. The most severe class of PBDs—Zellweger Spectrum Disorder (ZSD)—is caused by mutations in peroxin genes that result in both non-functional peroxisomes and mitochondrial dysfunction. It is unclear, however, how defective peroxisomes contribute to mitochondrial impairment. In order to understand the molecular basis of this inter-organellar relationship, we investigated the fate of peroxisomal mRNAs and proteins in ZSD model systems. We found that peroxins were still expressed and a subset of them accumulated on the mitochondrial membrane, which resulted in gross mitochondrial abnormalities and impaired mitochondrial metabolic function. We showed that overexpression of ATAD1, a mitochondrial quality control factor, was sufficient to rescue several aspects of mitochondrial function in human ZSD fibroblasts. Together, these data suggest that aberrant peroxisomal protein localization is necessary and sufficient for the devastating mitochondrial morphological and metabolic phenotypes in ZSDs.

2021-06-13 | GSE159869 | GEO

Gene expression profiles of hepatocyte-like cells derived from induced pluripotent stem cells (iPSCs) from donors with the Zellweger spectrum of peroxisome biogenesis disorders (PBD-ZSD) and healthy controls

2015-05-21 | GSE69066 | GEO

Project description:Skin fibroblasts from individuals with PBD-ZSD, a rare autosomal recessive disorder caused by peroxisome assembly defects, show defects in lipid metabolism that provide the basis for clinical diagnostic tests, but are not among the cell types most affected by disease. To explore phenotypes of more clinically relevant cell types, skin fibroblasts from PBD-ZSD patients and healthy controls were reprogrammed into iPS cells with all the hallmark properties of pluripotency. Subsequently, iPSCs were differentiated into ASGPR-positive hepatocyte-like cells that were subject to flow cytometry and subject to gene expression profiling. We report the gene expression profiles of hepatocyte-like cells derived from iPSCs that were themselves derived from skin fibroblasts from PBD-ZSD patient donors and healthy controls. The overall goal was to evaluate gene expression biomarkers of hepatocyte-like cells derived from PBD-ZSD patients and healthy controls. Dermal fibroblast cultures from 2 PBD-ZSD patients and 1 healthy control were reprogrammed into iPSCs by transfection with retroviruses designed to express the human OCT4, SOX2, KLF4 and c-MYC cDNA (see GEO entry GSE43996). Hepatic cell lineages were derived following the protocol of Duan (Duan Y, Catana A, Meng Y, Yamamoto N, He S, Gupta S et al. Stem Cells. 2007;25:3058-68; Duan Y, Ma X, Zou W, Wang C, Bahbahan IS, Ahuja TP et al. Stem Cells. 2010;28:674-86) with modifications. Total RNA samples from flow-sorted ASGPR-positive candidate hepatocyte-like cells obtained from healthy (control1) and PBD-ZSD patient (PBD_PEX1ms1 and PBD_PEX1fs1) donors were processed and analyzed on Affymetrix Human Genome 133A 2.0 microarrays.

2015-05-21 | E-GEOD-69066 | biostudies-arrayexpress

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