During development of the liver, cells progressively acquire all the properties that are specific to the organ. For instance, foetal liver cells are initially unable to produce glucose, but they acquire this capacity around birth. Similarly, the ducts which eliminate bile are formed in foetal liver but their structure reaches maturity only around birth.
Céline Demarez in the team of Frédéric Lemaigre now found that microRNA-337 is an important regulator of liver development. MicroRNA-337 controls maturation of hepatocytes and cholangiocytes, which are the cells exerting the liver's metabolic functions and which delineate the bile ducts, respectively.
MicroRNA-337 was found to belong to a network of genes which collectively control liver development. MicroRNA molecules are small non-coding RNA's that fine-tune the levels of proteins in a cell. They do this by restraining the translation of mRNA molecules into proteins.
Claude Gérard, an expert in mathematical modelling in the group of Frédéric Lemaigre, used computational tools to predict how microRNA-337 influences the gene network and controls liver development. Experiments with transgenic mice then confirmed the mathematical predictions.
The work is important for scientists producing liver cells in culture dishes for therapy of liver diseases. Fine-tuning protein expression is indeed necessary for production of safe and high quality cells for therapy. The work also illustrates the power of mathematical predictions as a tool to help designing successfull experiments.
MiR-337-3p controls hepatobiliary gene expression and transcriptional dynamics during hepatic cell differentiation
Demarez Céline, Gérard Claude, Cordi Sabine, Poncy Alexis, Achouri Younes, Dauguet Nicolas, Rosa David A., Gunning Patrick T., Manfroid Isabelle, Lemaigre Frédéric P.
Hepatology. 2017; doi: 10.1002/hep.29475 (ahead of print)