Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effect of depletion of Tfam on gene expression in stimulated B cells

ABSTRACT: The germinal centre (GC) reaction requires a unique bioenergetic supply. Although mitochondria are remodelled upon antigen stimulation, mitochondrial function in B cells is still poorly understood. To gain a better understanding of the role of mitochondria in B cell function, we generated a mice that lack, specifically in B cells, TFAM, a transcription factor necessary for mitochondrial biogenesis. TFAM knock-out (KO) mice displayed a blockage of the GC reaction and established an immune response featured by the differentiation of activated B cells towards memory B cells and aged-related B cells, hallmarks of an aged immune response. Unexpectedly, GC blockage in TFAM KO mice did not cause defects in the bioenergetic supply but this phenotype was associated with a defect in remodelling of the lysosomal compartment in B cells. Therefore, these results may describe a new mitochondrial function for antigen presentation during the GC reaction, the abrogation of which may be the basis of an aged immune response.

ORGANISM(S): Mus musculus

PROVIDER: GSE249893 | GEO | 2023/12/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Expression data for 2-month-old wild type and Tfam-SCKO (MPZ-Tfam KO) sciatic nerves

Project description:Gene expression analysis of 2-month-old Ctrl and Tfam-SCKO mice. At this age mitochondrial function is disrupted in the Schwann cells of Tfam-SCKO mice ,but their nerves display only very limited pathology. Mitochondrial dysfunction is a common cause of peripheral neuropathy. Much effort has been devoted to examining the role played by neuronal/axonal mitochondria, but how mitochondrial deficits in peripheral nerve glia (Schwann cells, SCs) contribute to peripheral nerve diseases remains unclear. Here, we investigate a mouse model of peripheral neuropathy secondary to SC mitochondrial dysfunction (Tfam-SCKOs). We show that disruption of SC mitochondria activates a maladaptive integrated stress response through actions of heme-regulated inhibitor kinase (HRI), and causes a shift in lipid metabolism away from fatty acid synthesis toward oxidation. These alterations in SC lipid metabolism result in depletion of important myelin lipid components as well as in accumulation of acylcarnitines, an intermediate of fatty acid b-oxidation. Importantly, we show that acylcarnitines are released from SCs and induce axonal degeneration. A maladaptive integrated stress response as well as altered SC lipid metabolism are thus underlying pathological mechanisms in mitochondria-related peripheral neuropathies. Total RNA samples were prepared by isolating and pooling RNA from three different 2-month-old MPZ-Tfam KO and Ctrl mice. 2 replicates per genotype were used in this experiment and they were prepared entirely independently.

2013-03-13 | E-GEOD-44605 | biostudies-arrayexpress

POLRMT regulates the switch between replication-primer formation and gene expression of mammalian mtDNA

Project description:Mitochondria are vital in providing cellular energy via their oxidative phosphorylation system, which requires the coordinated expression of genes encoded by both the nuclear and mitochondrial genomes (mtDNA). Transcription of the circular mammalian mtDNA depends on a single mitochondrial RNA polymerase (POLRMT). Although the transcription initiation process is well understood, it remains highly controversial if POLRMT also serves as the primase for initiation of mtDNA replication. In the nucleus, the RNA polymerases needed for gene expression have no such role. Conditional knockout of Polrmt in heart results in severe mitochondrial dysfunction causing dilated cardiomyopathy in young mice. We further studied the molecular consequences of different expression levels of POLRMT and found that POLRMT is essential for primer synthesis to initiate mtDNA replication in vivo. Furthermore, transcription initiation for primer formation has priority over gene expression. Surprisingly, mitochondrial transcription factor A (TFAM) exists in an mtDNA-free pool in the Polrmt knockout mice. TFAM levels remain unchanged despite strong mtDNA depletion and TFAM is thus protected from degradation of the AAA+ Lon protease in absence of POLRMT. Lastly, mitochondrial transcription elongation factor (TEFM) can compensate for a partial depletion of POLRMT in heterozygous Polrmt knockout mice, indicating a direct regulatory role for this factor in transcription. In conclusion, we present here the first in vivo evidence that POLRMT has a key regulatory role in replication of mammalian mtDNA and is part of a mechanism that provides a switch between RNA primer formation for mtDNA replication and mtDNA expression. Isolated heart mitochondria from three control mice (L/L) and three Polrmt knockout mice (L/L, cre), aged 3-4 weeks, were sequenced and analyzed for differential expression.

2016-08-05 | E-GEOD-83368 | biostudies-arrayexpress

ChIP-seq analysis of H3K27ac in K562 cells with shRNA-mediated depeltion of TFAM expression

Project description:The developing erythroid cells require highly coordinated gene expression and metabolism. By comparing the proteomic and transcriptomic changes in human hematopoietic stem/progenitor cells (HSPCs) and lineage-committed erythroid progenitors (ProEs), and uncover pathways related to mitochondrial biogenesis enhanced through post-transcriptional regulation. Two principal mitochondrial factors TFAM and PHB2 are tightly regulated at the protein level and indispensable for mitochondria and erythropoiesis. Depletion of TFAM in erythroid cells alters intracellular metabolism, leading to elevated histone acetylation, deregulated gene expression, defective mitochondria function and erythropoiesis.

2017-05-15 | GSE86864 | GEO

RNA-seq transcriptonal profiling in human primary adult erythroid progenitor cells (ProEs) after shRNA-mediated depletion of TFAM and PHB2 expression

Project description:The developing erythroid cells require highly coordinated gene expression and metabolism. By comparing the proteomic and transcriptomic changes in human hematopoietic stem/progenitor cells (HSPCs) and lineage-committed erythroid progenitors (ProEs), and uncover pathways related to mitochondrial biogenesis enhanced through post-transcriptional regulation. Two principal mitochondrial factors TFAM and PHB2 are tightly regulated at the protein level and indispensable for mitochondria and erythropoiesis. To determine the role of TFAM and PHB2 in mitochondrial function during erythroid development, we employed shRNA-mediated depeltion of TFAM and PHB2 expression in differentiating erythroid cells, and performed RNA-seq transcriptional profiling analysis.

2017-05-15 | GSE86910 | GEO

Tfam-deficiency mediated mitochondrial disorder affects Langerhans cell maintenance and function

Project description:Langerhans cells (LCs) are skin-resident professional antigen-presenting dendritic cells (DCs) to maintain skin homeostasis. The number and function of LCs are significantly reduced during the skin aging processes, which is closely related to the aging-associated skin disorders. However, the reasons underlying the changes of LC features with age are uncertain. Mitochondria are well known to be the main powerhouse to regulate cell fitness and function, and a decline in mitochondrial quality and activity was associated with normal aging and correlated with the development of a wide range of age-related diseases. So far, it is unknown if mitochondrial abnormality is involved in skin disorders by regulating LC homeostasis. The mitochondrial transcription factor A (Tfam) acts as a nuclear-encoded transcription factor and plays a critical role in mitochondrial stabilization. To explore the role of mitochondrial quality in LC homeostasis, we generated the mice with conditional deletion of Tfam in LC lineage. We found that Tfam-deficient LCs exhibits mitochondrial abnormality including morphology and membrane permeability of mitochondria, decreased cell number as well as maturation, whereas increased phagocytosis and inflammatory response of LCs. Interestingly, age-LCs from human skin have lower Tfam expression compared to young-LCs, and have the similar features with Tfam-deficient LCs analyzed by scRNA sequence (HRA000395). Thus, our data highlight that Tfam-mediated mitochondrial stability is essential for epidermal LC maintenance and function, which might be explain the states of increased susceptible to skin infections and rising incidence of cutaneous tumor in the elder. This is the first time to investigate the effect of mitochondria abnormality on LC homeostasis, which might be helpful for therapeutic interventions in aging-associated skin pathologies.

2022-08-13 | GSE202351 | GEO

RNA-seq transcriptonal profiling in E13.5 fetal liver erythroid cells from Tfam WT and KO mice

Project description:The developing erythroid cells require highly coordinated gene expression and metabolism. By comparing the proteomic and transcriptomic changes in human hematopoietic stem/progenitor cells (HSPCs) and lineage-committed erythroid progenitors (ProEs), and uncover pathways related to mitochondrial biogenesis enhanced through post-transcriptional regulation. Two principal mitochondrial factors TFAM and PHB2 are tightly regulated at the protein level and indispensable for mitochondria and erythropoiesis. To determine the role of TFAM in mitochondrial function during erythroid development, we generated Tfam conditional knockout (KO) mice by an erythroid-specific EpoR-Cre allele. We isolated the CD71+Ter119+ embryonic day (E)13.5 fetal liver erythroid cells by FACS sorting, and performed RNA-seq transcriptional profiling analysis.

2017-05-15 | GSE86865 | GEO

Expression data for 2-month-old wild type and Tfam-SCKO (MPZ-Tfam KO) sciatic nerves

2013-03-13 | GSE44605 | GEO

Oxygen sensitive regulation of TFAM linking the von Hippel-Lindau cancer syndrome to impaired mitochondrial biogenesis

Project description:The major consumers of oxygen in the cell are mitochondria. Here we identified an oxygen-sensitive regulation of TFAM, a key activator of mitochondrial transcription and replication. TFAM is hydroxylated by EglN3 on proline 53/56 and subsequently bound by the tumor suppressor von Hippel Lindau (pVHL). pVHL binding stabilizes TFAM by preventing mitochondrial LON proteolysis. Cells lacking wild-type VHL or in which EglN3 was inactivated genetically or by lack of oxygen have reduced mitochondria. All VHL cancer syndrome mutations tested, type 1, 2A, 2B, 2C, failed to bind hydroxylated TFAM, regardless of whether they have the ability to bind hydroxylated HIFa or not. In contrast, VHL-R200W polycythemia-mutation bound hydroxylated TFAM similar as wild-type VHL. VHL-R200W causes polycythemia with total absence of tumor development, despite increased HIFa signaling. Tumors of VHL related malignancies such as pheochromocytoma and renal carcinoma cells show low mitochondrial content, implicating that impaired mitochondrial biogenesis is linked to the malignancies of the VHL hereditary cancer syndrome.

2022-05-25 | PXD022734 | Pride

TFAM ChIP-seq in HeLa cells

Project description:ChIP-seq data characterizing the occupancy of TFAM over the mitochondrial and nuclear genomes in HeLa cells. Characterization of mitochondrial and nuclear genome-wide TFAM binding in HeLa cells

2013-09-21 | E-GEOD-48176 | biostudies-arrayexpress

RNA-seq transcriptional profiling in human primary fetal and adult CD34+ hematopoietic stem/progenitor cells (HSPCs) erythroid progenitor cells (ProEs)

Project description:Advances in sequencing-based genomic profiling present a new challenge of explaining how changes in DNA/RNA are translated into proteins linking genotypes to phenotypes. The developing erythroid cells require highly coordinated gene expression and metabolism, and serve as a unique model in dissecting regulatory events in development and disease. Here we compare the proteomic and transcriptomic changes in human hematopoietic stem/progenitor cells and lineage-committed erythroid progenitors, and uncover pathways related to mitochondrial biogenesis enhanced through post-transcriptional regulation. Two principal mitochondrial factors TFAM and PHB2 are tightly regulated at the protein level and indispensable for mitochondria and erythropoiesis. mTORC1 signaling is progressively enhanced to promote translation of mitochondrial proteins during erythroid specification. Genetic and pharmacological perturbation of mTORC1 or mitochondria impairs erythropoiesis. Our studies suggest a new mechanism for regulation of mitochondrial biogenesis through mTORC1-mediated protein translation, and may have direct relevance to the hematological defects associated with mitochondrial diseases and aging. Transcriptional profiling in human primary fetal and adult CD34+ hematopoietic stem/progenitor cells (HSPCs) erythroid progenitor cells (ProEs) by RNA-seq analysis.

2017-05-15 | E-GEOD-74053 | biostudies-arrayexpress

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