NAMPT/SIRT2-mediated inhibition of the p53-p21 signaling pathway is indispensable for maintenance and hematopoietic differentiation of human iPS cells

Abstract Background Nicotinamide phosphoribosyltransferase (NAMPT) regulates cellular functions through the protein deacetylation activity of nicotinamide adenine dinucleotide (NAD + )-dependent sirtuins (SIRTs). SIRTs regulate histones and none-histone proteins. The role NAMPT/SIRT pathway in regulation maintenance differentiation human-induced pluripotent stem (iPS) cells is not fully elucidated. Methods We evaluated effects specific inhibitors NAMPT or SIRT2 on pluripotency, proliferation, survival, hematopoietic human iPS cells. also studied molecular mechanism downstream NAMPT/SIRTs Results demonstrated that indispensable for maintenance, found inhibition induces p53 by promoting its lysine acetylation. This leads to activation target, p21, with subsequent cell cycle arrest induction apoptosis affect an embryoid body (EB)-based culture system. Conclusions Our data demonstrate essential NAMPT/SIRT2/p53/p21 signaling axis