New insights into redox regulation of stem cell self-renewal and differentiation

• ROS levels monitor the balance of stem cell self-renewal and differentiation.
• Redox sensors are the initial and direct executors of ROS signaling.
• Redox modifications of cysteine residues modulate protein function of redox sensors.
• Key regulators involved in stem cell self-renewal are recognized as redox sensors.

BackgroundReactive oxygen species (ROS), the natural byproducts of aerobic metabolism, are precisely orchestrated to evoke diverse signaling pathways. To date, studies have focused mainly on the detrimental effects of ROS in stem cells. Recently, accumulating evidence has suggested that ROS also function as second messengers that modulate stem cell self-renewal and differentiation by regulating intricate signaling networks. Although many efforts have been made to clarify the general effects of ROS on signal transduction in stem cells, less is known about the initial and direct executors of ROS signaling, which are known as ‘redox sensors’.Scope of reviewModifications of cysteine residues in redox sensors are of significant importance in the modulation of protein function in response to different redox conditions. Intriguingly, most key molecules in ROS signaling and cell cycle regulation (including transcriptional factors and kinases) that are crucial in the regulation of stem cell self-renewal and differentiation have the potential to be redox sensors.Major conclusionsWe highlight herein the importance of redox regulation of these key regulators in stem cell self-renewal and differentiation.General significanceUnderstanding the mechanisms of redox regulation in stem cell self-renewal and differentiation will open exciting new perspectives for stem cell biology. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation.