Calcium signaling as an integrator and decoder of niche factors to control somatic stem cell quiescence and...

Somatic stem cells (SSCs) play a major role in tissue homeostasis and respond to a panoply of micro-environmental cues by adjusting their quiescence and activation profiles. How these cells integrate and decode multiple niche signals remains elusive. In recent years, Ca²⁺ signaling has emerged as one of the key intracellular pathways that allow stem cells to dynamically adjust their fate and either to remain quiescent for future needs or to become activated to generate new progeny. Interestingly, not only distinct Ca²⁺ signatures are associated with the quiescence and activation states of stem cells, but also various extracellular cues impinge on Ca²⁺ pathways to dynamically regulate the responses of stem cells to different niche signals. This Viewpoint article deals with how Ca²⁺ signaling may be used to decode and integrate different niche factors and how Ca²⁺ fluctuations of distinct amplitudes, frequencies, and overall intracellular levels may trigger the differential gene transcription program. Knowledge about mechanisms that allow SSCs to translate the complexity of extracellular niche signaling into intrinsic states of cell quiescence and activation is crucial for understanding life-long tissue homeostasis and regeneration.