Epigenetic Switching by the Metabolism-sensing Factors in the Generation of Orexin Neurons from Mouse Embryonic Stem Cells

Hayakawa, Koji; Hirosawa, Mitsuko; Tabei, Yasuyuki; Arai, Daisuke; Tanaka, Satoshi; Murakami, Noboru; Yagi, Shusuke; Shiota, Kunio

doi:10.1074/jbc.m113.455899

Cited by 71 publications

(71 citation statements)

References 60 publications

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“…O-GlcNAcylation modifications appear to influence the determination of specific neuronal identity. During mESC differentiation, OGA co-localizes with the histone acetyltransferase p300 on the neuropeptide encoding gene orexin in orexin neurons, while OGT co-localizes with histone deacetylase sirtuin 1 (SIRT1) in non-orexin expressing cells (65). Due to the direct link between HBP and O-GlcNAcylation, we propose that metabolic fluctuations induced by specific microenvironmental differentiation drivers, such as hypoxia, could participate in establishing distinct epigenome patterns associated with cell fate and function acquisitions and maintenance.…”

Section: O-glcnacylationmentioning

confidence: 99%

“…The hexosamine biosynthesis pathway (HBP) is a nutrient-sensing pathway that depends on glucose, glutamine, and cytosolic Ac-CoA levels (Figure 2 Conversely, a decrease in O-GlcNAcylation disrupts self-renewal and reprogramming (57), but promotes differentiation in neuronal cells (63)(64)(65). Moreover, CPTFs such as OCT4 and SOX2 harbor an O-GlcNAcylation motif that is quickly erased upon differentiation (57).…”

Section: Hexosamine Biosynthesis and Fate Transitionsmentioning

confidence: 99%

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Metabolism in pluripotency: Both driver and passenger?

Dahan

Nguyen

et al. 2019

Journal of Biological Chemistry

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Downloaded from2 Pluripotent stem cells (PSCs) are highly proliferative cells characterized by robust metabolic demands to power rapid division. For many years considered a passive component or "passenger" of cell fate determination, cell metabolism is now starting to take center stage as a driver of cell fate outcomes. This review provides an update and analysis of our current understanding of PSC metabolism and its role in self-renewal, differentiation, and somatic cell reprogramming to pluripotency. Moreover, we present evidence on the active roles metabolism plays in shaping the epigenome to influence patterns of gene expression that may model key features of early embryonic development.Most investigators view metabolism, which encompasses the synthesis and utilization of macromolecules and energy, as a passive supporter of self-renewal and rapid proliferation in pluripotent stem cells (PSCs) 1 and their differentiated, slower dividing progeny. However, exciting recent studies are changing this perception by showing an active role for metabolism in PSC fate determination.

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Section: O-glcnacylationmentioning

confidence: 99%

Section: Hexosamine Biosynthesis and Fate Transitionsmentioning

confidence: 99%

Metabolism in pluripotency: Both driver and passenger?

Dahan

Nguyen

et al. 2019

Journal of Biological Chemistry

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“…ManNAc has been shown to successfully generate functional orexin neurons from mouse ESCs, and the key step in the differentiation pathway is an epigenetic switch on histones from a hypoacetylated state with unidentified OGlcNAcylated nuclear proteins to a hyperacetylated state at T-DMRs. ManNAc causes the dislocation of Ogt/Sirt1/Sin3A/ Ezh2 from the T-DMRs of the Hcrt gene locus and the recruitment of p300, CBP, and Mgea5 [108].…”

Section: Cell Fate Determination Of Neuronal Subtypes By Sirt1mentioning

confidence: 99%

SIRT1 and Neural Cell Fate Determination

Cai

et al. 2015

Mol Neurobiol

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During the development of the central nervous system (CNS), neurons and glia are derived from multipotent neural stem cells (NSCs) undergoing self-renewal. NSC commitment and differentiation are tightly controlled by intrinsic and external regulatory mechanisms in space- and time-related fashions. SIRT1, a silent information regulator 2 (Sir2) ortholog, is expressed in several areas of the brain and has been reported to be involved in the self-renewal, multipotency, and fate determination of NSCs. Recent studies have highlighted the role of the deacetylase activity of SIRT1 in the determination of the final fate of NSCs. This review summarizes the roles of SIRT1 in the expansion and differentiation of NSCs, specification of neuronal subtypes and glial cells, and reprogramming of functional neurons from embryonic stem cells and fibroblasts. This review also discusses potential signaling pathways through which SIRT1 can exhibit versatile functions in NSCs to regulate the cell fate decisions of neurons and glia.

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“…Intriguingly, OGA is a bifunctional enzyme harboring O-GlcNAc cleavage activity as well as HAT activity, implying an intrinsic relationship between histone O-GlcNAcylation and acetylation. OGA HAT activity has been implicated in orexin neurogenesis [43]. However, we are just beginning to understand the function of histone O-GlcNAcylation as part of the epigenetic code.…”

Section: Protein O-glcnacylation In Epigeneticsmentioning

confidence: 99%

O-GlcNAc signaling in cancer metabolism and epigenetics

et al. 2015

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The covalent attachment of β-D-N-acetylglucosamine monosaccharides (O-GlcNAc) to serine/threonine residues of nuclear and cytoplasmic proteins is a major regulatory mechanism in cell physiology. Aberrant O-GlcNAc modification of signaling proteins, metabolic enzymes, and transcriptional and epigenetic regulators has been implicated in cancer. Relentless growth of cancer cells requires metabolic reprogramming that is intertwined with changes in the epigenetic landscape. This review highlights the emerging role of protein O-GlcNAcylation at the interface of cancer metabolism and epigenetics.

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Epigenetic Switching by the Metabolism-sensing Factors in the Generation of Orexin Neurons from Mouse Embryonic Stem Cells

Cited by 71 publications

References 60 publications

Metabolism in pluripotency: Both driver and passenger?

Metabolism in pluripotency: Both driver and passenger?

SIRT1 and Neural Cell Fate Determination

O-GlcNAc signaling in cancer metabolism and epigenetics

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