Abstract
Aerobic glycolysis is one of the most important common characteristics in both cancer cells and stem cells. Metabolism switch has been discovered as an important early event in the process of reprogramming somatic cells to induced pluripotent stem cells (iPSCs). As a rate limiting kinase in glycolysis, Pkm2 has been reported playing critical roles in many tumors, yet its role in stem cells and iPSCs induction is poorly defined. In the present study, we showed that Pkm2 is a predominant pyruvate kinase in embryonic stem cells (ESCs), and its expression increases many pluripotent genes. During somatic cell reprogramming, up-regulation of Pkm2 can be observed and over-expression of Pkm2 can facilitate iPSCs induction, while Pkm1 or a mutant form of Pkm2 (Pkm2K422R) showed no enhancement role in iPSCs induction. Therefore, our data demonstrated that Pkm2 enhances the pluripotency maintenance in ESCs and promotes the pluripotency acquisition during somatic cell reprogramming.
Highlights
By ectopically expressing Oct4, Sox2, Klf4 and c-Myc, somatic cells can be reprogrammed into induced pluripotent stem cells [1]
The expression of Pkm2 decreased along with embryonic stem cells (ESCs) differentiation which is similar to the pluripotent gene Nanog (Figure 1C)
We found that Pkm2 which prior to exist as a dimer conformation with lower pyruvate kinase activity facilitated the induced pluripotent stem cells (iPSCs) induction while Pkm1 and Pklr didn’t (Figure 5B)
Summary
By ectopically expressing Oct, Sox, Klf and c-Myc, somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) [1]. Embryonic stem cells (ESCs) possess distinct metabolic features compared with somatic cells [5]. Somatic oxidative bioenergetics transition into aerobic glycolysis is participated and facilitates reprogramming [6]. Catalyzing the transfer of a phosphate group from phosphoenolpyruvate (PEP) to ADP producing pyruvate and ATP, which is a rate-limiting step in glycolysis, Pkm has been found highly express in aggressive tumors and play important roles in tumor metabolism, growth and migration [10,11,12,13,14]. Distinct from its splicing analogue Pkm, Pkm was found prefer the lower activity dimer form, which could facilitate the accumulation of semi-products for www.impactjournals.com/oncotarget anabolic demands in tumor cells [15]. It is interesting to elucidate the role of Pkm in normal tissues especially ESCs which share many similar features to tumor cells
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