Knockdown of AT-rich interaction domain (ARID) 5B gene expression induced AMPKα2 activation in cardiac myocytes

Hirose-Yotsuya, Lisa; Okamoto, F; Yamakawa, Toshio; Whitson, Robert H.; Fujita‐Yamaguchi, Yoko; Itakura, Keiichi

doi:10.5582/bst.2015.01159

Cited by 3 publications

(1 citation statement)

References 32 publications

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“…Arid5b is known as a regulator of metabolism in pre-adipocytes, adipocytes, muscles and NK cells affecting glycolysis and oxidative phosphorylation (35,(38)(39)(40)54). To investigate the effect of Arid5b ablation on metabolism of Pre-B cells, we isolated B220 + B cells from BM, cultured in the presence of IL-7 for 72 hours, and measured extracellular acidification rate (ECAR) and oxidation consumption ratio (OCR) using a Seahorse metabolic flux analyzer.…”

Section: Arid5b Regulates Fatty Acid Oxidation In Pre-b Cellsmentioning

confidence: 99%

ARID5B regulates fatty acid metabolism and proliferation at the Pre-B cell stage during B cell development

et al. 2023

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During B cell development in bone marrow, large precursor B cells (large Pre-B cells) proliferate rapidly, exit the cell cycle, and differentiate into non-proliferative (quiescent) small Pre-B cells. Dysregulation of this process may result in the failure to produce functional B cells and pose a risk of leukemic transformation. Here, we report that AT rich interacting domain 5B (ARID5B), a B cell acute lymphoblastic leukemia (B-ALL) risk gene, regulates B cell development at the Pre-B stage. In both mice and humans, we observed a significant upregulation of ARID5B expression that initiates at the Pre-B stage and is maintained throughout later stages of B cell development. In mice, deletion of Arid5b in vivo and ex vivo exhibited a significant reduction in the proportion of immature B cells but an increase in large and small Pre-B cells. Arid5b inhibition ex vivo also led to an increase in proliferation of both Pre-B cell populations. Metabolic studies in mouse and human bone marrow revealed that fatty acid uptake peaked in proliferative B cells then decreased during non-proliferative stages. We showed that Arid5b ablation enhanced fatty acid uptake and oxidation in Pre-B cells. Furthermore, decreased ARID5B expression was observed in tumor cells from B-ALL patients when compared to B cells from non-leukemic individuals. In B-ALL patients, ARID5B expression below the median was associated with decreased survival particularly in subtypes originating from Pre-B cells. Collectively, our data indicated that Arid5b regulates fatty acid metabolism and proliferation of Pre-B cells in mice, and reduced expression of ARID5B in humans is a risk factor for B cell leukemia.

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Section: Arid5b Regulates Fatty Acid Oxidation In Pre-b Cellsmentioning

confidence: 99%

ARID5B regulates fatty acid metabolism and proliferation at the Pre-B cell stage during B cell development

et al. 2023

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Spatiotemporal Gene Coexpression and Regulation in Mouse Cardiomyocytes of Early Cardiac Morphogenesis

Liu

Wang

et al. 2018

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Cardiac looping is an early morphogenic process critical for the formation of four-chambered mammalian hearts. To study the roles of signaling pathways, transcription factors (TFs) and genetic networks in the process, we constructed gene co-expression networks and identified gene modules highly activated in individual cardiomyocytes (CMs) at multiple anatomical regions and developmental stages. Function analyses of the module genes uncovered major pathways important for spatiotemporal CM differentiation. Interestingly, about half of the pathways were highly active in cardiomyocytes at outflow tract (OFT) and atrioventricular canal (AVC), including many well-known signaling pathways for cardiac development and several newly identified ones. Most of the OFT-AVC pathways were predicted to be regulated by 66 transcription factors (TFs) actively expressed at the OFT-AVC locations, with the prediction supported by motif enrichment analysis of the TF targets, including 10TFs that have not been previously associated with cardiac development, e.g., Etv5, Rbpms, and Baz2b. Finally, our study showed that the OFT-AVC TF targets were significantly enriched with genes associated with mouse heart developmental abnormalities and human congenital heart defects.All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

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Spatiotemporal Gene Coexpression and Regulation in Mouse Cardiomyocytes of Early Cardiac Morphogenesis

Liu

Wang

et al. 2019

JAHA

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BackgroundHeart tube looping to form a 4‐chambered heart is a critical stage of embryonic heart development, but the gene drivers and their regulatory targets have not been extensively characterized at the cell‐type level.Methods and ResultsTo study the interaction of signaling pathways, transcription factors (TFs), and genetic networks in the process, we constructed gene co‐expression networks and identified gene modules highly activated in individual cardiomyocytes at multiple anatomical regions and developmental stages using previously published single‐cell RNA‐seq data. Function analyses of the modules uncovered major pathways important for spatiotemporal cardiomyocyte differentiation. Interestingly, about half of the pathways were highly active in cardiomyocytes at the outflow tract (OFT) and atrioventricular canal, including well‐known pathways for cardiac development and many newly identified ones. We predicted that these OFT‐atrioventricular canal pathways were regulated by a large number of TFs actively expressed at the OFT–atrioventricular canal cardiomyocytes, with the prediction supported by motif enrichment analysis, including 10 TFs that have not been previously associated with cardiac development (eg, Etv5, Rbpms, and Baz2b). Furthermore, we found that TF targets in the OFT–atrioventricular canal modules were most significantly enriched with genes associated with mouse heart developmental abnormalities and human congenital heart defects, in comparison with TF targets in other modules, consistent with the critical developmental roles of OFT.ConclusionsBy analyzing gene co‐expression at single cardiomyocytes, our systematic study has uncovered many known and additional new important TFs and their regulated molecular signaling pathways that are spatiotemporally active during heart looping.

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Knockdown of AT-rich interaction domain (ARID) 5B gene expression induced AMPKα2 activation in cardiac myocytes

Cited by 3 publications

References 32 publications

ARID5B regulates fatty acid metabolism and proliferation at the Pre-B cell stage during B cell development

ARID5B regulates fatty acid metabolism and proliferation at the Pre-B cell stage during B cell development

Spatiotemporal Gene Coexpression and Regulation in Mouse Cardiomyocytes of Early Cardiac Morphogenesis

Spatiotemporal Gene Coexpression and Regulation in Mouse Cardiomyocytes of Early Cardiac Morphogenesis

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