CRG: 'Yin and Yang' switch lies at the heart of animal stem cells

CRG: 'Yin and Yang' switch lies at the heart of animal stem cells

News from CRG

A molecular switch that flips between different versions of genes could be crucial for maintaining stem cells across all animals from simple flatworms to humans, according to a study from scientists at the Centre for Genomic Regulation (CRG) in Barcelona, published today, in the journal eLife.

Flatworms (also known as planarians) have an incredible capacity for self-renewal, with almost any part of their body able to regenerate a whole new worm in a matter of days. In collaboration with Jordi Solana and Nikolaus Rajewsky and other colleagues from the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) in Germany and the University of Toronto, CRG group leader Manuel Irimia studied the patterns of gene activity in stem cells in these unusual animals.

They found that they ‘mix and match’ certain parts of their genes in particular ways – a process known as alternative splicing*. The same analysis of flatworm cells that had changed (differentiated) into more specific cell types revealed a different mixture of gene parts.

Looking more closely, the team discovered that two families of molecules – CELF and MBNL – work as a kind of ‘yin and yang’ switch, enabling cells to flip between different patterns of alternative splicing. CELF molecules guide gene splicing patterns linked to self-renewal of stem cells, while MBNL factors favour differentiation.

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Jordi Solana, Manuel Irimia, Salah Ayoub, Marta R. Orejuela, Vera Zywitza, Marvin Jens, Javier Tapial, Debashish Ray, Quaid D. Morris, Timothy R. Hughes, Benjamin J. Blencowe, Nikolaus Rajewsky. 
“Conserved functional antagonism of CELF and MBNL proteins controls stem cell-specific alternative splicing in planarians.” 
eLife, August 9, 2016.