Stem cell switch unearthed in flatworms

Researchers studying flatworms have discovered a ‘ying and yang’ switch that allows for the creation or specialisation of stem cells.

A specific genus of flatworm, Planaria, has the unusual distinction of being able to regenerate almost any part of their body. This ability enables them to be cut into many small pieces with a new worm growing from each individual piece within a matter of days.

Researchers discovered that the flatworms assembled certain parts of their genes in a particular way, known as alternative splicing. There were two families of molecules they discovered — CELF and MBNL — that enabled either the self-renewal or differentiation of stem cells. CELF molecules were found to guide gene splicing patterns linked to the renewal of stem cells while MNBL induced cell differentiation.

Manuel Irimia, group leader at the Centre for Genomic Regulation (CGR) in Barcelona, said: “Discovering that this kind of alternative splicing mechanism exists across such a wide evolutionary range suggests that it is very ancient, and may be equally important as transcription factors for giving animal stem cells their unique properties.”

In mammals, transcription factors are responsible for maintaining embryonic stem cells. They do not play the same role in the stem cells of invertebrates such as flatworms which split off from the ancestral line of mammals about 600 million years ago.

Irimia said: “Understanding how this 'yin and yang' switch is flipped and activates particular patterns of alternative splicing could one day lead to more improved methods for generating and differentiating stem cells, which could be used be used for regenerative medicine.”

The study was carried out alongside researchers from the Max Delbrück Center for Molecular Medicine in Germany and the University of Toronto.

The research was published in eLife.