Distinct Regulation of Phosphoribosyl Pyrophosphate Synthetase(PRPS) isoforms in Embryonic Stem Cells

Abstract

Stem cells have distinct features in metabolism compared with differentiated somatic cells and metabolism is important in stem cells. Because stem cells divide very actively and nucleotide is essential for cell division, metabolism related to nucleotide in stem cells is expected to be different from that in somatic cells. Thus, in ESCs, nucleotide metabolism will be important in maintaining stemness and thus, regulated by some pluripotency factors. Phosphoribosyl Pyrophosphate Synthetase (PRPS) is an enzyme that makes Phosphoribosyl Pyrophosphate (PRPP) from Ribose-5phosphate in nucleotide biosynthesis pathways. Since PRPP is used in both purine and pyrimidine biosynthesis pathways, PRPS enzyme is important in nucleotide metabolism. PRPS has two isoforms, PRPS1 and PRPS2 which are known to have differences in many diseases and cancers. However, PRPS isoforms are little understood in stem cells. In this study, we investigated how Prps1 and Prps2 are regulated and the functional differences between them in ESCs. First, we observed that the expression patterns of Prps1 and Prps2 were different during ESC differentiation. And pluripotency factors like Oct4, Sox2, and Nanog (OSN) were mainly occupied in Prps1 promoters. Next, we observed different knockdown phenotypes through each Prps1 and Prps2-knockdown ESCs. In consequence, Prps1 is a stronger target of Oct4, Sox2, and Nanog which is mainly regulated in stem cells. And, based on different knockdown phenotypes, Prps1 and Prps2 have functional differences in addition to common function making PRPP in ESCs.