EMC: Theory of regenerativity

Author: David Kent, 10/28/13

Last Friday was the final day of the Till & McCulloch Meetings in Banff, which was a great display of collaborative stem cell projects going on across the country. I’ll emphasize again how wonderful this meeting is for getting a broad survey of research in adult and pluripotent stem cells without having to wade through thousands of people and posters. It also includes Canada’s leading stem cell policy and ethics circles and has a nice flavor of biomedical engineering collaborations that are really pushing the boundaries of what can be imagined.

In the morning we were treated to some delightful unpublished data from Michael Underhill that charts his lab’s work from initial discovery of an interesting molecule in skeletal muscle all the way through to an elegant series of lineage tracing experiments showing their role in supporting cellular regeneration.

The first experiments identified a protein (named EMC) that was expressed in a rare population of cells that upon drug-induced injury, expanded into the space created. This prompted the Underhill group to create an EMC reporter mouse (basically this involves adding a fluorescent molecule onto the protein) to observe what happened throughout normal development. A comprehensive analysis of the reporter mouse was performed to assess which tissues expressed EMC and what happened upon injury. These studies concluded that EMC marked a primitive cell population that bore many features of a multipotent mesenchymal stromal cell.

The multiple cell types that mesenchymal stromal cells should make are numerous, but loosely fall into the categories of marrow stromal, cartilage, tendon, and fat cells. Underhill showed convincing data demonstrating that the activated EMC labeled cells were present in all of these cell types making them an excellent candidate for a multipotent stromal cell population. Interestingly, while they tried very hard to find them, the EMC positive cells could not be shown to make muscle cells.

For me, the nicest experiments were in a model of damaged pancreatic tissue that showed damaged areas compared to undamaged areas with EMC positive cells flooding the damaged portions but not the undamaged areas.

Overall, it seems that EMC marks a population of quiescent multipotent mesenchymal cells that are driven into action when regeneration is required. Underhill suspects that they create a supportive environment for the proliferation and differentiation of required cell types. A small subset of these cells go back into hibernation as a reserve for the next round of injury. Underhill also described evidence that EMC was upregulated in breast cancer pointing at a potential role for EMC in the tumour microenvironment.

The question period was also quite interesting. In particular, Underhill was asked whether he thought EMC positive cells were associated with scar tissue rather than being a definitive supporting cell and what sort of molecules might be mediating the supportive qualities of the cells. Also, in order to see if single clones can drive the multiple lineages, crosses to the confetti reporter mouse would be important to demonstrate. While there is clearly some work to do, this first description of a protein that marks a quiescent population of highly regenerative multipotent mesenchymal stromal cells is incredibly exciting. Can’t wait to see the paper in print!

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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/research/pis/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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