Translational regulation of hepatogenic differentiation

PhD thesis defended by Marino CARUSO (Prof. Patsy RENARD) - 15/07/2021

Prof. Patsy RENARD, UNamur, NARILIS (promoter)

Dr. Mustapha NAJIMI, UCLouvain, IREC (co-promoter)

  • ARNOULD Thierry (UNamur), président
  • RENARD Patricia (UNamur), secrétaire et promotrice
  • VERFAILLIE Catherine (KULeuven)
  • CLOSE Pierre (ULiège)
  • HAMER Isabelle (UNamur)
  • NAJIMI Mustapha (UCLouvain)

Translational regulation is of paramount importance for proteome remodelling during stem cell differentiation both at the global and transcript-specific levels. Previous results generated by our group in a model of human bone-derived mesenchymal stem cells (hBM-MSCs) hepatogenic differentiation suggests that translational regulation could participate to hepatocyte differentiation. In this work, we took advantage of a more robust induced pluripotent stem cells (iPSCs) model to characterize translational remodelling during hepatogenic differentiation by polysome profiling. We demonstrate that protein synthesis increases during exit from pluripotency, and is then globally repressed during later steps of hepatogenic maturation. This global downregulation of translation is accompanied by a decrease in the protein abundance of components of the translation machinery, which involves a global reduction in translational efficiency of terminal oligopyrimidine tract (TOP) mRNAs encoding translation-related factors. Despite global translational repression during hepatogenic differentiation, key hepatogenic genes remain efficiently translated, and the translation of several transcripts involved in hepato-specific functions and metabolic maturation are even induced. We conclude that, during hepatogenic differentiation, a global decrease in protein synthesis is accompanied by a specific translational rewiring of hepato-specific transcripts.