Apr 13, 2020

Differential localization patterns of pyruvate kinase isoforms in murine naïve, formative and primed pluripotent states

BioRxiv : the Preprint Server for Biology
J. G. DierolfDean H Betts

Abstract

Mouse embryonic stem cells (mESCs) and mouse epiblast stem cells (mEpiSCs) represent opposite ends of a pluripotency continuum, referred to as naive and primed pluripotent states, respectively. These divergent pluripotent states differ in several ways including growth factor requirements, transcription factor expression, DNA methylation patterns, and metabolic profiles. Naive cells employ both glycolysis and oxidative phosphorylation (OXPHOS), whereas primed cells preferentially utilize aerobic glycolysis, a trait shared with cancer cells referred to as the Warburg effect. Until recently, metabolism has been regarded as a by-product of cell fate; however, evidence now supports metabolism as being a driver of stem cell state and fate decisions. Pyruvate kinase muscle isoforms (PKM1 and PKM2) are important for generating and maintaining pluripotent stem cells (PSCs) and mediating the Warburg effect. Both isoforms catalyze the last step of glycolysis generating adenosine triphosphate and pyruvate, however, the precise role(s) of PKM1/2 in naive and primed pluripotency is not well understood. The primary objective was to characterize the cellular expression and localization patterns of PKM1 and PKM2 in mESCs, chemically transitione...Continue Reading

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