The Relevance of Circadian Clocks to Stem Cell Differentiation and Cancer Progression

The molecular mechanism of circadian clocks depends on transcription-translation feedback loops (TTFLs) that have known effects on key cellular processes. However, the distinct role of circadian TTFLs in mammalian stem cells and other less differentiated cells remains poorly understood. Neural stem cells (NSCs) of the brain generate neurons and glia postnatally but also may become cancer stem cells (CSCs), particularly in astrocytomas. Evidence indicates clock TTFL impairment is needed for tumor growth and progression; although, this issue has been examined primarily in more differentiated cancer cells rather than CSCs. Similarly, few studies have examined circadian rhythms in NSCs. After decades of research, it is now well recognized that tumors consist of CSCs and a range of other cancer cells along with noncancerous stromal cells. The circadian properties of these many contributors to tumor properties and treatment outcome are being widely explored. New molecular tools and ones in development will likely enable greater discrimination of important circadian and non-circadian cells within malignancies at multiple stages of cancer progression and following therapy. Here, we focus on adult NSCs and glioma CSCs to address how cells at different stages of differentiation may harbor unique states of the molecular circadian clock influencing differentiation and cell fate.