The importance of unequal division in stem cells

Author: David Kent, 04/30/13

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Stem cells must strike a balance between different types of divisional outcomes in order to provide the correct numbers and types of cells for the lifetime of an organism. At each cell division, a stem cell either makes two replicates of itself to expand the population (a self-renewal division), makes two highly proliferating cells to meet the body’s immediate demands for cells (a differentiation division) or one of each (asymmetric division). If we create too many stem cells, our bodies will not have sufficient specialized cells to do the day-to-day jobs and if we have too few, then the system will exhaust itself.

In most adult stem cell populations (e.g. blood, skin, etc), the goal is to balance these types of divisions, keeping a sufficient stem cell reserve while also producing differentiated daughter cells to supply the system each day. On an individual cell basis, the easiest way to maintain this balance is to have stem cells divide asymmetrically. But how does a cell mechanically arrange itself to distribute different components to one daughter compared to the other?  Earlier this month I attended a special Royal Society meeting in London focused on cellular polarity where leading scientists came together to discuss how cells arrange themselves. This free meeting was an excellent mix of new technological advances and lessons from developmental biology that stem cell biologists should be aware of when thinking about asymmetric division.

The conference emphasized the importance of actin and myosin in the control of establishing polarity in cells with presentations from multiple different tissues and model organisms. The discussions ranged from the modeling of chemical movements through membranes to the decoupling of the machinery used for yeast bud site selection from that involved in bud formation.

The most exciting presentation in my opinion was given by Orion Weiner of UCSF, who used optogenetics to study membrane tension in blood cells. In essence, he showed the ability to pull selected proteins to the membrane by turning a light on and off. He showed that pulling actin toward the plasma membrane increases the membrane tension and alters the behaviour of molecules located long distances from the membrane. Most importantly, future experiments that can specifically control the location, timing and amount of particular proteins on one side of a cell will allow biologists to study the impact of proteins on the asymmetric partitioning of molecules in a cell.

From a stem cell biologist’s point of view, this is exactly the kind of tool that we could use to understand the role of various proteins in the asymmetric partitioning of stem cell determinants and it will be exciting to see how this technology is applied in the future.

Additional information and the proof of principle experiments can be found in the original Nature paper and lead authour Anselm Levskaya has set up a neat website with videos for how this light controlled protein modulation works.

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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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