Circadian clocks: from stem cells to tissue homeostasis and regeneration

Abstract

The circadian clock is an evolutionarily conserved timekeeper that adapts body physiology to diurnal cycles of around 24 h by influencing a wide variety of processes such as sleep‐to‐wake transitions, feeding and fasting patterns, body temperature, and hormone regulation. The molecular clock machinery comprises a pathway that is driven by rhythmic docking of the transcription factors BMAL1 and CLOCK on clock‐controlled output genes, which results in tissue‐specific oscillatory gene expression programs. Genetic as well as environmental perturbation of the circadian clock has been implicated in various diseases ranging from sleep to metabolic disorders and cancer development. Here, we review the origination of circadian rhythms in stem cells and their function in differentiated cells and organs. We describe how clocks influence stem cell maintenance and organ physiology, as well as how rhythmicity affects lineage commitment, tissue regeneration, and aging.

Icariin promotes osteogenic differentiation of BMSCs by upregulating BMAL1 expression via BMP signaling

“…in fact, a circadian clock exists in every cell of the human body. The central players in these are BMal1 encoded by the gene arnTl and clock circadian regulator (clocK) by the gene clocK (19). BMScs are stem cells with the ability to differentiate in vitro into adipocytes, osteoblasts and cartilage-forming chondroblasts (20).…”

SR9009 has REV-ERB–independent effects on cell proliferation and metabolism

“…REV-ERB | circadian rhythms | SR9009 | ligand | specificity T he cell-autonomous circadian clock regulates a plethora of physiological processes in the human body (1)(2)(3). The importance of proper clock maintenance is highlighted by linkages between circadian desynchrony and a variety of illnesses, including sleep and metabolic disorders, cardiovascular diseases, and cancer (1,2,(4)(5)(6)(7). This has fueled recent interest in the circadian clock as a therapeutic target (8)(9)(10)(11)(12).…”

P19 Cells as a Model for Studying the Circadian Clock in Stem Cells before and after Cell Differentiation

“…One hypothesis states that the clock does not oscillate, or that it is non-functional in stem cells to allow them to grow faster than differentiated cells [34353637]. Our findings suggest that oscillation of clock genes may be present in certain stem cells, and in future this information could be used as biomarkers to differentiate between different stem cell types.…”

“…A functional clock is present in adult stem cells. Here, circadian oscillations have a clear impact on driving proliferation and differentiation, thus enhancing both tissue homeostasis and regeneration [35]. Many in vitro studies have shown that pluripotent cells have no obvious rhythmicity, but their differentiated counterparts – even multipotent neural precursor cells (NPCs) – have robust circadian oscillations [36].…”