Sequencing of Aldh2-/- Adh5-/- mouse HSPC clones
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB40375 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR4593410_1.fastq.gz | Fastqsanger.gz | |||
| ERR4593410_2.fastq.gz | Fastqsanger.gz | |||
| ERR4593420_1.fastq.gz | Fastqsanger.gz | |||
| ERR4593420_2.fastq.gz | Fastqsanger.gz | |||
| ERR4593411_1.fastq.gz | Fastqsanger.gz |
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Project description:We investigated the ALDH2*2 genetic polymorphism and its underlying mechanisms for the first time in a human model system of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from individuals carrying the most common heterozygous form of the ALDH2*2 genotype. We showed that the ALDH2*2 mutation confers elevated levels of reactive oxygen species (ROS) and toxic aldehydes such as 4HNE, thereby inducing cell cycle arrest and activation of apoptotic signaling pathways, especially during ischemic injury. ALDH2 exerts control of cell survival decisions via modulation of oxidative stress levels. This regulatory circuitry was found to be dysfunctional in the loss-of-function ALDH2*2 genotype, causing upregulation of apoptosis in cardiomyocytes following ischemic insult. These results reveal a novel function of the metabolic enzyme ALDH2 in modulation of cell survival decisions. Molecular mechanism of increased ischemic damage in cardiomyocytes of ALDH2*2 genotype.
2014-07-07 | E-GEOD-59100 | biostudies-arrayexpress
Project description:ALDH2 activator, Alda-1, is able to increase the catalytic activity of ALDH2. ALDH2 expression negatively correlates with obesity in mice while 4-HNE accumulation is positively associated with obesity and is increased in terminal adipocyte differentiation. We compared the difference of transcription profile between ethanol (EtOH)-treated and Alda-1-treated cells in induced adipocyte differentiation of 3T3-L1 pre-adipocytes.
2016-09-07 | E-MTAB-4936 | biostudies-arrayexpress
Project description:We investigated the ALDH2*2 genetic polymorphism and its underlying mechanisms for the first time in a human model system of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from individuals carrying the most common heterozygous form of the ALDH2*2 genotype. We showed that the ALDH2*2 mutation confers elevated levels of reactive oxygen species (ROS) and toxic aldehydes such as 4HNE, thereby inducing cell cycle arrest and activation of apoptotic signaling pathways, especially during ischemic injury. ALDH2 exerts control of cell survival decisions via modulation of oxidative stress levels. This regulatory circuitry was found to be dysfunctional in the loss-of-function ALDH2*2 genotype, causing upregulation of apoptosis in cardiomyocytes following ischemic insult. These results reveal a novel function of the metabolic enzyme ALDH2 in modulation of cell survival decisions.
2014-07-07 | GSE59100 | GEO
Project description:mRNA levels of MHCCLM3 cell line over expressing ALDH2 and GFP were evaluated with Aligent microarray
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Project description:In the McSC lineage in zebrafish, Aldh2 activity is an important source of formate through its metabolism of its substrate formaldehyde. This formate is required as input into the folate cycle, in particular de novo purine biosynthesis. This scRNA-seq experiment was conducted to investigate the global effects of Aldh2 inhibition on the transcriptomes of isolated McSCs.
2022-05-09 | GSE183868 | GEO
Project description:The tumor suppressor p53 is critical for tumor suppression and other biological events. Yet, the regulatory role of p53 in alcohol-induced fatty liver remains unclear. Here, we show a role for p53 in regulating the ethanol metabolism via acetaldehyde dehydrogenase 2 (ALDH2), a key enzyme responsible for oxidization of alcohol. Through repressing ethanol oxidization, p53 suppresses intracellular levels of acetyl-CoA and histone acetylation, leading to the inhibition of the stearoyl-CoA desaturase-1 (SCD1) gene expression. Mechanistically, p53 directly binds to ALDH2 and prevents the formation of its active tetramer, and indirectly limits the production of pyruvate that promotes the activity of ALDH2. Notably, p53 deficient mice exhibit increased lipid accumulation, which can be reversed by ALDH2 depletion. Moreover, hepatic specific knockdown of SCD1 diminishes ethanol-induced fatty liver caused by p53 loss. By contrast, overexpression of SCD1 in liver promotes ethanol-induced fatty liver development in wildtype mice, while has mild effect on p53-/- or ALDH2-/- mice. Overall, our findings reveal a previously unrecognized function of p53 in alcohol-induced fatty liver, and uncover pyruvate as a natural regulator of ALDH2.
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Project description:Purpose: upper tract urothelial carcinoma (UTUC) is the predominant subtype of the renal pelvis carcinoma but current knowledge about the molecular properties and prognostic markers is sparse. In this study, we examined the genome-wide mRNA expression spectrum of UTUC aiming to characterize the molecular basis of this cancer, and identify potential prognostic markers and thus facilitate the clinical practices. Experimental Design: we compared the whole mRNA expression spectrum of cancer and matched normal tissues in 10 patients with UTUC using massively parallel sequencing, thereafter the protein levels and prognostic roles of ALDH2, CCNE1 and SMAD3 were evaluated under an independent validation set comprising of 104 patients. Results: mRNA down-regulation of ALDH2 and up-regulation of SMAD3 and CCNE1 in UTUC were revealed by expression profiling. And low protein expression of ALDH2 was associated with an adverse outcome for patients (p < 0.0001). Whereas high CCNE1 and SMAD3 were associated with adverse clinical outcome (p < 0.0001). And multivariate analysis revealed that all these three molecular markers were independent prognostic predictors. Besides, compared to the pathological TNM classification, All ALDH2, CCNE1 and SMAD3 were more competent in identifying patient subgroup with high mortality risk, and the molecular markers were able to predict the survival difference in the patients of T2 and T3 subgroup (p < 0.001), which could not be achieved by TNM staging. Conclusions: This is the first prospective study that characterizes genome-wide mRNA expression profile of UTUC. We revealed the prognostic significance of ALDH2, CCNE1 and SMAD3, and these molecular marker were more robust than TNM system in clinical outcome prediction.
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Project description:With domain focused CRISPR screen, we revealed Fanconi anemia (FA) proteins UBE2T (an E2) and FANCL (an E3) as unique dependencies in AML. We demonstrate that these dependencies are due to a synthetic lethal interaction between FA proteins and Aldehyde Dehydrogenase 2 (ALDH2), which function in parallel pathways to counteract the genotoxic effects of endogenous aldehydes. We provide evidence that DNA hypermethylation and transcriptional silencing of ALDH2 occur in a recurrent manner in human AML patient samples, which is sufficient to confer FA pathway dependency in this disease. Taken together, our study suggests that targeting of the ubiquitination reaction catalyzed by FA proteins can eliminate ALDH2-deficient AML.
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Project description:Whole genome sequencing of mouse sarcoma clones
2024-05-24 | GSE208366 | GEO
Project description:Obesity and type 2 diabetes have reached pandemic proportion. In particular, the population with diabetes is expected to rise rapidly in East and South Asia. ALDH2 (acetaldehyde dehydrogenase 2, mitochondrial) is the key metabolizing enzyme of acetaldehyde and other toxic aldehydes, such as 4-hydroxynonenal (4-HNE).
A missense Glu504Lys mutation of the ALDH2 gene is prevalent in 560 million East Asians, resulting in reduced ALDH2 enzymatic activity. We found that Aldh2 knock-in (KI) mice mimicking human Glu504Lys mutation were prone to develop diet-induced obesity, glucose intolerance, insulin resistance, and fatty liver compared with controls due to reduced adaptive thermogenesis and energy expenditure.
We found elevated 4-HNE levels and increased 4-HNE adducted proteins due to reduced activity of ALDH2 of the brown adipose tissue (BAT) from the Aldh2 homozygous KI mice. Proteomic analyses of the BAT from the Aldh2 KI mice identified increased 4-HNE-adducted proteins involved in mitochondrial fatty acid oxidation (FAO) and electron transport chain (ETC), leading to markedly decreased FAO and mitochondrial respiration of BAT, which is essential for adaptive thermogenesis and energy expenditure.
AD-9308 is a water-soluble prodrug of a potent and highly selective ALDH2 activator AD-5591. In vitro, AD-5591 enhanced both WT and mutant ALDH2 enzymatic activities. AD-9308 allosterically activates ALDH2 mainly by partially blocking the substrate exit tunnel, thereby accelerating the substrate-enzyme collision.4-HNE-adducted proteins, especially those involved in mitochondrial fatty acid beta-oxidation and electron transfer chain of the brown adipose tissue from the Aldh2 knock-in mice, leading to impaired mitochondrial dysfunction brown adipose tissue. In vivo, AD-9308 treatment reduced serum 4-HNE levels, ameliorated diet-induced obesity and fatty liver, and improved glucose homeostasis in both Aldh2 WT and KI mice dose-dependently. Our data highlight the therapeutic potential of reducing toxic aldehyde levels by activating ALDH2 for treating metabolic diseases.
2023-04-16 | MSV000091724 | MassIVE