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.

Cancer stem cell generation during epithelial-mesenchymal transition is temporally gated by intrinsic circadian clocks.

Epithelial-mesenchymal transition (EMT) is a key event preceding tumor cell metastasis that increases cell invasiveness and cancer stem cell (CSC) populations. Studies suggest that genes used in generating circadian rhythms also serve in regulating EMT. To test the role of circadian clocks in cellular EMT events two cancer cell lines were compared, one that has a well-established circadian clock, C6 from rat glioma, and one that does not, MCF-7 from human breast tumor.

Musashi-2 and related stem cell proteins in the mouse suprachiasmatic nucleus and their potential role in circadian rhythms.

Background: The suprachiasmatic nucleus (SCN) of the mammalian hypothalamus contains the master circadian clock of the body and an unusually large number of cells expressing stem cell-related proteins. These seemingly undifferentiated cells may serve in entrainment of the SCN circadian clock to light cycles or allow it to undergo neural plasticity important for modifying its rhythmic output signals. These cells may also proliferate and differentiate into neurons or glia in response to episodic stimuli or developmental events requiring alterations in the SCN's control of physiology and behavior.

A Meta-Analysis Characterizing Stem-Like Gene Expression in the Suprachiasmatic Nucleus and Its Circadian Clock.

Cells expressing proteins characteristic of stem cells and progenitor cells are present in the suprachiasmatic nucleus (SCN) of the adult mammalian hypothalamus. Any relationship between this distinctive feature and the master circadian clock of the SCN is unclear. Considering the lack of obvious neurogenesis in the adult SCN relative to the hippocampus and other structures that provide neurons and glia, it is possible that the SCN has partially differentiated cells that can provide neural circuit plasticity rather than ongoing neurogenesis.