Elusive key molecular signal for planarian stem cell regeneration identified.

Like a magician, the freshwater flatworm known as planaria can survive decapitation or even being cut into many pieces. Its ability to fully regenerate from tiny remnants of tissue is due to a special population of adult stem cells known as neoblasts.  Scientists have spent decades studying the mechanisms that drive this remarkable feat, with the hopes that any secrets they uncover might lead to new perspectives in human biology and new ways to treat disease.  Now, a study from researchers at the Stowers Institute identifies a key molecule that directs stem cells in the planarian flatworm to make copies of themselves.  The team state that their findings have important implications for advancing regenerative medicine and for developing more effective cancer therapies.  The opensource study is published in the journal Developmental Cell.

Previous studies show that planarians are world-renowned for their regenerative properties. Split one down the middle, and two identical organisms will appear in its place. Cut a fragment 1/279th the size of the original animal and it will regenerate a complete animal. This ability originates in a special group of adult stem cells called neoblasts that are spread throughout the bodies of these freshwater worms. Several years ago, researchers tested the limits of these resilient creatures by subjecting them to near-lethal doses of radiation. They found that even if just a single neoblast remained, it was enough to replenish the entire population of planarian stem cells.  The current study identifies a molecule, known as EGFR-3, which is part of a cascade of signals that seem to control the way these cells divide and differentiate in response to near-lethal levels of radiation.

The current study utilised an advanced molecular technique called RNA interference to silence different genes in the suspected signaling pathways.  The planaria were then given a dose of radiation that would kill most, but not all, of their resident neoblasts.  Results show that the egfr-3 gene is required for neoblast repopulation. The lab explain that this gene codes for a protein that sits on the surface of cells and binds another protein, called epidermal growth factor, known to stimulate growth, proliferation, and differentiation in other cell types.

The group state that they confirmed their findings by using a fluorescent staining to illuminate the EGFR-3 protein on the neoblasts; data findings show that the proteins sat on the top of the cell and were clumped together on one side.  They go on to add that the uneven distribution of EGFR-3 suggested that the protein might be involved in a phenomenon known as asymmetric cell division, where the mother cell divides into two daughter cells that have different fates, one might be a neoblast, another a muscle cell or photoreceptor cell.

The team surmise that their study shows stem cell repopulation can be achieved from even a single pluripotent stem cell in planarian flatworms.  They go on to add that even though asymmetric cell division has long been proposed to exist in planarians, their study provides the first direct molecular evidence of its existence.  For the future, the researchers believe that this particular pathway might be providing a type of quality control to ensure that mistakes made to the genome either through irradiation or other forms of damage are not propagated.  They conclude that the theory would be that only the cells with the best DNA get to stick around and serve as the template for future generations, something they need to test next.

Source: Stowers Institute for Medical Research


This image shows asymmetric stem cell division in a planarian flatworm showing a smaller cell with DNA (labeled in red) and a larger cell with a stem cell marker (smedwi-1 RNA, labeled in green). Scale bar is 10 micrometers.  Credit: Sánchez Alvarado Lab.

This image shows asymmetric stem cell division in a planarian flatworm showing a smaller cell with DNA (labeled in red) and a larger cell with a stem cell marker (smedwi-1 RNA, labeled in green). Scale bar is 10 micrometers. Credit: Sánchez Alvarado Lab.




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