Regulation of Stem Cell Function by NAD

Nicotinamide adenine dinucleotide (NAD⁺), a coenzyme in cellular metabolism, has never ceased to capture the fascination of scientists since its discovery in 1906. The expansion of NAD⁺'s function from cellular metabolism to DNA repair, gene regulation, cell signaling, and aging reflects the central role of cellular metabolism in orchestrating the diverse cellular pathways. In the past decade, NAD⁺ has emerged as a key regulator of stem cells, opening the door to potential approaches for regenerative medicine. Here we reflect on how the field of NAD⁺ regulation of stem cells has evolved since a decade ago, when sirtuins, NAD⁺-dependent enzymes, were shown to be critical regulators of stem cells. We review the recent development on how NAD⁺ is regulated in stem cells to influence fate decision. We discuss the difference in NAD⁺ regulation of normal and cancer stem cells. Finally, we consider the consequences of NAD⁺ regulation of stem cells for health and diseases.