Debasree, Dutta (2017) Histone chaperone in regulation of cellular metabolism dictating stem cell fate? Stem cell investigation, 4 (50). ISSN 2313-0792

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Abstract

Cellular metabolism could regulate pluripotent states of embryonic stem cells (ESC) mediated by metabolites (1). These metabolites simultaneously could dictate the fate of pluripotent states through epigenetic modifications. Dynamicity in expression of three different metabolites namely, acetate, S-adenosylmethionine and O-linked β-N-acetylglucosamine facilitate the regulation of epigenetic landscape and thus influence the fate of ESCs and the pluripotent states (1). Human ESCs and mouse EpiESCs exist in a primed state of pluripotency in comparison to the naïve state of pluripotency in mouse ESCs (2). Colony morphologies, response to signaling pathways, contribution to generate chimera, epigenetic states and cellular metabolism distinctively divides these two states of pluripotency (2). Primed ESCs predominantly utilize glycolysis whereas naïve ESCs exploit a bivalent metabolism, switching between glycolysis and oxidative phosphorylation on demand as major source of energy (3). α-Ketoglutarate (α-KG), an intermediate product of TCA cycle, has been shown to enhance pluripotency in mouse ESCs while inhibit differentiation by blocking DNA and histone demethylation (4). But, in hESCs, increased α-KG level accelerated initial differentiation while an induced succinate level delayed differentiation, implying a context specific role in cell fate determination (5). Metabolites, including α-KG, serve as cofactor to regulate dioxygenase enzymes associated with epigenetic modifications. Exploiting the concept of metabolism, small molecules targeting metabolic pathways have been proved to rescue mitochondrial DNA mutation by manipulation of pluripotent stem cells (6). So, a better understanding in regulation of pluripotency by epigenetic modification through metabolites will further enrich the field of regenerative medicine.

Item Type:	Article
Subjects:	Cancer Research
Depositing User:	Central Library RGCB
Date Deposited:	03 Nov 2017 06:39
Last Modified:	03 Nov 2017 06:39
URI:	http://rgcb.sciencecentral.in/id/eprint/493

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