Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

FASN-dependent de novo lipogenesis is required for brain development

ABSTRACT: Fate and behaviour of neural progenitor cells is tightly regulated during mammalian brain development. Metabolic pathways, such as glycolysis and oxidative phosphorylation, that are required for supplying energy and providing molecular building blocks to generate cells, govern progenitor function. However, the role of de novo lipogenesis, which is the conversion of glucose into fatty acids through the multi-enzyme protein fatty acid synthase (FASN), for brain development remains unknown. Using Emx1Cre-mediated, tissue-specific deletion of Fasn in the mouse embryonic telencephalon, we show that loss of FASN causes severe microcephaly, largely due to altered polarity of apical, radial glia progenitors (APs) and reduced progenitor proliferation. Further, genetic deletion and pharmacological inhibition of FASN in human embryonic stem cell (ESC)-derived forebrain organoids identifies a conserved role of FASN-dependent lipogenesis for radial glia cell polarity and progenitor expansion in the developing human forebrain. Thus, our data establish a role of de novo lipogenesis for mouse and human brain development and identify a link between progenitor cell polarity and lipid metabolism.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Neuronal Stem Cell

SUBMITTER: Daniel Gonzalez

LAB HEAD: Sebastian Jessberger

PROVIDER: PXD026110 | Pride | 2022-01-14

REPOSITORIES: pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	20210323_002_S285769_EtOH_500cells_DIA_Rep1_S2-A1_1_1500.d.zip	Other
	20210323_003_S285771_CER_24h_500cells_DIA_Rep1_S2-B1_1_1501.d.zip	Other
	20210323_005_S285771_CER_24h_500cells_DIA_Rep2_S2-B2_1_1503.d.zip	Other
	20210323_006_S285769_EtOH_500cells_DIA_Rep2_S2-A2_1_1504.d.zip	Other
	20210323_009_S285769_EtOH_500cells_DIA_Rep3_S2-A3_1_1507.d.zip	Other

Items per page:

1 - 5 of 10

Similar Datasets

Metabolic control of adult neural stem cell activity by FASN-dependent lipogenesis

Project description:Mechanisms controlling the proliferative activity of neural stem/progenitor cells (NSPCs) play a pivotal role to ensure life-long neurogenesis in the mammalian brain. How metabolic programs are coupled with NSPC activity remains unknown. Here we show that fatty acid synthase (FASN), the key enzyme of de novo lipogenesis, is highly active in adult NSPCs and that conditional deletion of FASN in NSPCs impairs adult neurogenesis. The rate of de novo lipid synthesis and subsequent proliferation of NSPCs is regulated by Spot14, a gene we found to be selectively expressed in low proliferating adult NSPCs. Spot14 reduces the availability of malonyl-CoA, which is an essential substrate for FASN to fuel lipogenesis. Thus, we here identified a functional coupling between the regulation of lipid metabolism and adult NSPC proliferation. 6 samples were analyzed. Spot14+: Spot14 GFP positive mouse neural stem cell, 3 biological rep Spot14-: Spot14 GFP negative mouse neural stem cell, 3 biological rep

2012-11-02 | E-GEOD-27391 | biostudies-arrayexpress

Metabolic control of adult neural stem cell activity by FASN-dependent lipogenesis

2012-11-02 | GSE27391 | GEO

Brain region differences in α1 and α5 subunit-containing GABAA receptor proteome revealed by affinity purification and Blue Native PAGE proteomics

Project description:GABAA receptors are the major inhibitory receptors in the brain. They are hetero-pentamers with a composition of predominantly two α, two β and one γ or δ subunit. From the six α subunit genes, the α5 subunit displays a limited spatial expression pattern and is known to mediate both phasic and tonic inhibition. In this study, using immunoaffinity-based proteomics we identified the α5 subunit containing receptor complexes in hippocampus and olfactory bulb. The α1-α5 interaction was identified in both brain regions albeit with significantly different stoichiometries. In line with this, reverse IPs using anti-α1 antibody showed the α5-α1 co-occurrence and validated the quantitative difference. In addition, we showed that the association of Neuroligin 2 with α1-containing receptors was much higher in olfactory bulb than hippocampus, which was confirmed using blue native gel electrophoresis and quantitative mass spectrometry. Finally, immunocytochemical staining revealed co-localization of α1 and α5 subunits in post-synaptic puncta in the hippocampus.

2024-01-26 | PXD047550 | Pride

Targeting cancer-derived extracellular vesicles by combining CD147 inhibition and tissue factor pathway inhibitor for the management of urothelial cancer cells

Project description:Cancer cells release small particles or vesicles, which have the potency to induce cancer cells to spread and grow. In this study, we focused on two molecules presented by cell-derived vesicles that might promote cancer cells spread: a clotting protein and a cell surface protein. We found that vesicles from bladder cancer cells that could spread had higher levels of these proteins than vesicles from cancer cells that could not spread. We also found that these vesicles could make cancer cells move about more, produce more of a substance that helps cancer cells spread, and invade other tissues. To counteract the cancer-promoting actions of vesicles, we examined the impact of combining a naturally occurring anti-clotting protein that can be released by medications derived from heparin. We found that the combination could stop the vesicles from making cancer cells move about more, produce more of the spreading substance, and invade other tissues. These findings suggest that combining the inhibitor with medications derived from heparin to induce the release of the anti-clotting protein might be a new way to treat bladder cancer.

2024-05-21 | PXD044680 | Pride

Genome-wide analysis of fatty acid synthase (FASN) gene silenced normal liver cells (THLE 2) using cDNA microarray analysis

Project description:Fatty acid synthase is a major enzyme involved in de novo lipogenesis, associated with energy homeostasis, lipid storage and signalling in normal liver cells. The effect of fatty acid synthase knockdown in normal liver cells (THLE 2) using siRNA mediated gene silencing were assesed for global gene deregulations. The deregulated metabolism, cell signalling and cell cycle pathway related gene expressions were analysed. Statistical significance values were also recorded. This expermental analysis clearly points to a important biochemical role for FASN in normal liver cell physiology. Total RNA was extracted from the THLE 2 cells transfected with FASN siRNA at 48h, along with its untransfected control cells. cDNA converted samples were run on microarray platform- Illumina HumanHT-12 V4.0 expression beadchip

2016-06-02 | E-GEOD-82096 | biostudies-arrayexpress

Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use

Project description:Metabolic diseases are closely linked to aberrant synthesis of endogenous fatty acids in the liver, called de novo lipogenesis (DNL), which is mediated by the enzyme fatty acid synthase (FASN). The composition of complex lipids consists of saturated or monosaturated fatty acids, which can be endogenously produced, and polyunsaturated fatty acids (PUFA), which are strictly dietary. Compositional differences between individuals are insufficiently understood and may influence the onset and progression of metabolic and cardiovascular diseases. Here we show that DNL critically determines the use of dietary PUFA. A patient with a hypofunctional heterozygous de novo Arg2177Cys variant in FASN exhibited an elevated composition of PUFA, which was phenocopied by pharmacological inhibition of FASN with TVB-2640 in patients with nonalcoholic steatohepatitis (NASH). In mice, the incorporation rate of supplemented omega-3 PUFA during an obesogenic diet was increased by genetic or pharmacologic reduction of DNL. Mechanistically, we show that the FASN variant exhibited a cysteine-dependent, non-enzymatic acetylation of FASN, which resulted in hyperubiquitinylation and decreased protein stability. Our study further reveals that PUFA storage is an active, enzymatic process controlled by FASN, diacylglycerol O-acyltransferase 2 (DGAT2) and MFSD2A, a membrane-transport protein, and that combining FASN inhibition and PUFA supplementation exerts additive beneficial metabolic effects. These findings provide evidence that the success of PUFA supplementation may depend on the rate of endogenous DNL and that combined PUFA supplementation and FASN inhibition may be a promising approach targeting metabolic disease.

2023-12-19 | PXD045908 | Pride

Proteome of Caco-2 cells, transfected with KRAS-G12D and stimulated with different conditions.

Project description:Description: (Supplemental data for Project PXD035399) “Analysis of context-specific KRAS-effectors (sub)complexes in Caco-2 cells”. Proteome of Caco-2 cells, transfected with KRAS-G12D and stimulated with different conditions.

2023-02-23 | PXD039404 | Pride

Mus musculus

Project description:Metabolic control of adult neural stem cell activity by FASN-dependent lipogenesis

| PRJNA137007 | ENA

Comparative DDA and DIA-PASEF proteomics profiling of cross-kingdom macrophage infection reveals new mechanisms driving pathogen virulence

Project description:Opportunistic infections of the respiratory tract often succeed under a weakened immune response caused by an underlying illness or hospitalization. The human fungal pathogen, Cryptococcus neoformans, and the bacterial pathogen, Klebsiella pneumoniae, are both well-characterized microbes that cause severe infections within immunocompromised individuals. In this study, we simulate a concentration-dependent pulmonary coinfection of a bacterial and fungal pathogen, and profile the proteomic changes by DDA vs. DIA. Dual perspective profiling provides new insights into host defense regulation of infection and pathogenic mechanisms of invasion.

2024-08-13 | PXD054527 | Pride

Full proteome analysis of Hoxb8 immortalized murine myeloid progenitors knockout for CCDC134 and differentiated into macrophages

Project description:We recently identified CCDC134 as a novel regulator of TLR responses. To gain a comprehensive understanding of the effects of CCDC134 loss, we conducted total proteome analysis on control sgRen and sgCCDC134 Hoxb8 immortalized murine myeloid progenitors that were differentiated into macrophages. Interestingly, we observed that plasma membrane and endolysosomal TLRs, along with their associated chaperone Gp96, were among the most significantly downregulated proteins. Our findings further demonstrated that CCDC134 is essential for the proper folding and stability of Gp96. As a result, the deletion of CCDC134 in various cell lines and Hoxb8-derived macrophages results in altered TLR folding and trafficking.

2024-11-14 | PXD053042 | Pride