Transthyretin orchestrates vitamin B12-induced stress resilience
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ABSTRACT:
PROVIDER: PRJNA1109405 | ENA |
REPOSITORIES: ENA
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Project description:Background: Chronic stress significantly contributes to mood- and anxiety disorders. Previous data suggest a correlative connection between vitamin B12 supplementation, depression, and stress resilience. However, the underlying mechanisms are still poorly understood. Methods: Using the chronic variable stress mouse model coupled with RNA-sequencing, we determined vitamin B12-induced transcriptional changes related to stress resilience. By viral-mediated gene transfer and in vivo epigenome editing, we reveal a functional pathway linking vitamin B12, DNA methylation, and depressive-like symptoms. Results: We identified Transthyretin (Ttr) as a sex-specific key target of vitamin B12 action in chronic stress. Accordingly, TTR expression was increased postmortem in the prefrontal cortex of male, but not female, depressed patients. Virally altered Ttr in the prefrontal cortex functionally contributed to stress- and depression-related behaviors, changes in dendritic spine morphology, and gene expression. In stressed mice, vitamin B12 reduced DNAme in the Ttr promoter region. Importantly, using in vivo epigenome editing to alter DNAme in the brains of living mice for the first time, we establish a direct causal link between DNAme on Ttr and stress-associated behaviors. Discussion: In summary, using state-of-the-art techniques, this study uncovers a mechanistic link between cobalamin supplementation, Ttr, and markers of chronic stress and depression, encouraging further studies into dietary interventions for mood disorders.
2024-05-13 | GSE267047 | GEO
Project description:Transthyretin orchestrates vitamin B12-induced stress resilience [II]
| PRJNA1111103 | ENA
Project description:Background: Chronic stress significantly contributes to mood- and anxiety disorders. Previous data suggest a correlative connection between vitamin B12 supplementation, depression, and stress resilience. However, the underlying mechanisms are still poorly understood. Methods: Using the chronic variable stress mouse model coupled with RNA-sequencing, we determined vitamin B12-induced transcriptional changes related to stress resilience. By viral-mediated gene transfer and in vivo epigenome editing, we reveal a functional pathway linking vitamin B12, DNA methylation, and depressive-like symptoms. Results: We identified Transthyretin (Ttr) as a sex-specific key target of vitamin B12 action in chronic stress. Accordingly, TTR expression was increased postmortem in the prefrontal cortex of male, but not female, depressed patients. Virally altered Ttr in the prefrontal cortex functionally contributed to stress- and depression-related behaviors, changes in dendritic spine morphology, and gene expression. In stressed mice, vitamin B12 reduced DNAme in the Ttr promoter region. Importantly, using in vivo epigenome editing to alter DNAme in the brains of living mice for the first time, we establish a direct causal link between DNAme on Ttr and stress-associated behaviors. Discussion: In summary, using state-of-the-art techniques, this study uncovers a mechanistic link between cobalamin supplementation, Ttr, and markers of chronic stress and depression, encouraging further studies into dietary interventions for mood disorders.
2024-05-18 | GSE267339 | GEO
Project description:Elucidation of new roles for vitamin B12 in regulation of folate, ubiquinone, and methionine metabolism
2018-10-22 | PXD005723 | Pride
Project description:Astrocytes express a vitamin B12 uptake receptor, CD320/TCblR, that is regulated by S1P1 signaling. In search of genes controlled under B12 deficiency in astrocytes, we employed RNA-seq using RNA of astrocytes cultured in normal or B12 deficient media.
2022-05-17 | GSE99113 | GEO
Project description:Vitamin B12 (B12) is an important cofactor in mycobacterial metabolism, and some pathogenic mycobacteria need to obtain it from the host. In this study, we investigated the transport of vitamin B12 in Mycobacterium marinum. We identified a transcriptor regulator that could be potentially involved in the uptake process. RNA sequencing analysis were performed in order to elucidate the regulon of this new transcriptor.
2023-08-14 | GSE240448 | GEO
Project description:Examination of the impact of vitamin B12 supplementation during in vitro OSKM reprogramming
2023-08-07 | GSE200579 | GEO
Project description:Pseudomonas aeruginosa undergoes cell elongation and forms robust biofilms during anaerobic respiratory growth using nitrate (NO3-) as an alternative electron acceptor. Understanding the mechanism of cell shape change induced upon anaerobiosis is crucial to the development of effective treatments against P. aeruginosa biofilm infection. Anaerobic growth of PAO1 reached higher cell density in the presence of vitamin B12, an essential coenzyme of class II ribonucleotide reductase. In addition, cell morphology returned to a normal rod shape. These results suggest that vitamin B12, the production of which was suppressed during anaerobic growth, can restore cellular machineries for DNA replication and therefore facilitate better anaerobic growth of P. aeruginosa with normal cell division. We used microarray to elucidate the global gene expression profiles underlying vitamin B12-induced changes in bacterial cell shape and growth-associated properties. Gene expression profiles of PAO1 grown in LBN (LB+NO3-) or LBN supplemented with 1 microM vitamin B12 are compared.
2012-06-17 | E-GEOD-34836 | biostudies-arrayexpress
Project description:Recent functional genomics and genome-scale modeling approaches indicated that B12 production in Lactobacillus reuteri could be improved by medium optimization. Here we show that a series of systematic single amino acid omissions could significantly modulate the production of B12 from nearly undetectable levels (by isoleucine omission) to 20-fold higher than previously reported through omission of cysteine. We analyzed by cDNA microarray experiments the transcriptional response of L. reuteri to the medium lacking cysteine. These results supported the observed high B12 production and provided new avenues for future improvement of production of vitamin B12. Keywords: cell type comparison loop design
2010-05-17 | E-GEOD-13391 | biostudies-arrayexpress
Project description:Recent functional genomics and genome-scale modeling approaches indicated that B12 production in Lactobacillus reuteri could be improved by medium optimization. Here we show that a series of systematic single amino acid omissions could significantly modulate the production of B12 from nearly undetectable levels (by isoleucine omission) to 20-fold higher than previously reported through omission of cysteine. We analyzed by cDNA microarray experiments the transcriptional response of L. reuteri to the medium lacking cysteine. These results supported the observed high B12 production and provided new avenues for future improvement of production of vitamin B12. Keywords: cell type comparison
2008-10-31 | GSE13391 | GEO