Tick, tock, clock – the clock is ticking for you

Author: David Kent, 12/06/11

From the depths of the poetic frivolity of Raphael de la Ghetto come some words that might help guide us through one of the most interesting concepts being pursued by stem cell biologists these days.  Specifically, research has emerged which links stem cell behaviour and fate choices to circadian rhythm. The group of Salvador Aznar Benitah in Barcelona recently published research which links skin stem cell turnover and heterogeneity to the body’s internal clock. Their work has inspired many new studies that aim to understand the impacts of circadian rhythm on other stem cell systems.

In tissues that have high turnover (such as the skin, gut, and blood), daily oscillating changes in the balance between making more stem cells (self-renewal) vs. more specialized cells (differentiation) seems a reasonable method for regulating cell number and type. Whether or not these effects are occurring in the stem cells themselves is not fully understood, as stem cells are often regarded as a reservoir of inactive cells that are typically only used when other cell types are in high demand. Furthermore, scientists have known about Clock and Bmal1, two proteins that play a leading role in circadian pacemaking, since 1994 and 2000 respectively, but a strong link to stem cell fate choice had not been made until this paper.

When the ticks turn to tocks

While the Fresh Prince may have had ulterior motives in his recitation, geneticists have made careers from turning ticks into tocks – taking genes away or turning them on inappropriately in order to gain knowledge of genetic functions. The Aznar Benitah study showed that the removal of a major “clock” protein (Bmal1) disturbed the balance of stem cell division and dormancy, which is critical for maintaining the correct balance of stem cells and more mature progenitors. This disturbance in rhythm led to premature ageing as well as an increased incidence of tumours, suggesting that we might better understand how cancers grow and progress by understanding the natural cycles our bodies go through. Aznar Benitah himself discusses this midway through a YouTube clip on his research (start at the 1:56 minute mark for a great description of the research)

Knocking at your door

Where does this leave us? For one thing, this study and others have stimulated a push to understand the relationship of stem cells, transcription, and metabolism, which will undoubtedly lead to interesting discoveries in how our body’s tissues achieve the balance required for lifelong production of the correct numbers and types of specialized cells. However, we should be quite cautious moving forward as this research sits on the interface between the hyped field of stem cell research and a vast catalogue of metabolism altering products (e.g.: pills for weight loss, energy boosting, or anti-aging) and I worry that many a seller of snake oil are laying in the bush, devising ways to take advantage of the links between the two.

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David Kent

David Kent

Principal Investigator at University of Cambridge
Dr. David Kent is a Principal Investigator at the University of Cambridge in the Cambridge Stem Cell Institute (http://www.stemcells.cam.ac.uk/researchers/principal-investigators/dr-david-kent). His laboratory's research focuses on fate choice in single blood stem cells and how changes in their regulation lead to cancers. David is currently the Stem Cell Institute’s Public Engagement Champion and has a long history of public engagement and outreach including the creation of The Black Hole in 2009. He has been writing for Signals since 2010.
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