Nicotinamide Promotes Cell Survival and Differentiation as Kinase Inhibitor in Human Pluripotent Stem Cells

Abstract

Summary: Nicotinamide, the amide form of vitamin B3, is widely used in disease treatments and stem cell applications. However, nicotinamide's impact often cannot be attributed to its nutritional functions. In a vitamin screen, we find that nicotinamide promotes cell survival and differentiation in human pluripotent stem cells. Nicotinamide inhibits the phosphorylation of myosin light chain, suppresses actomyosin contraction, and leads to improved cell survival after individualization. Further analysis demonstrates that nicotinamide is an inhibitor of multiple kinases, including ROCK and casein kinase 1. We demonstrate that nicotinamide affects human embryonic stem cell pluripotency and differentiation as a selective kinase inhibitor. The findings in this report may help researchers design better strategies to develop nicotinamide-related stem cell applications and disease treatments. : In this report, Guokai Chen and colleagues show that nicotinamide is a kinase inhibitor with multiple targets. Nicotinamide improves human pluripotent stem cell (hPSC) survival as a ROCK inhibitor, and it also induces hPSC differentiation as a casein kinase 1 inhibitor. This discovery highlights nicotinamide's regulatory function beyond its common roles in metabolism, PARP, and sirtuin pathways. Keywords: nicotinamide, human pluripotent stem cell, cell survival, cell differentiation, kinase inhibitor