@article{254f3b790da34079aae433b82f44bab4,
title = "The global downregulation of protein synthesis observed during hepatogenic maturation is associated with a decrease in TOP mRNA translation",
abstract = "Translational regulation is of paramount importance for proteome remodeling during stem cell differentiation at both the global and the transcript-specific levels. In this study, we characterized translational remodeling during hepatogenic differentiation of induced pluripotent stem cells (iPSCs) 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 abundance of protein components of the translation machinery, which involves a global reduction in translational efficiency of terminal oligopyrimidine tract (TOP) mRNA 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 hepatospecific functions and metabolic maturation is even induced. We conclude that, during hepatogenic differentiation, a global decrease in protein synthesis is accompanied by a specific translational rewiring of hepatospecific transcripts.",
keywords = "hepatocyte differentiation, iPSC, LARP1, polysome profiling, stem cells, TOP mRNA, translational regulation",
author = "Marino Caruso and S{\'e}bastien Meurant and Damien Detraux and Amandine Mathieu and Manon Gilson and Marc Dieu and Antoine Fattaccioli and Catherine Demazy and Mustapha Najimi and Etienne Sokal and Thierry Arnould and Catherine Verfaillie and Lafontaine, {Denis L.J.} and Patricia Renard",
note = "Funding Information: We would like to thank Ola Larsson and Christian Oertlin (Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden) for their help with polysome profiling data analysis and critical comments on the manuscript. We would also like to thank Ludivine Wacheul (RNA Molecular Biology, ULB, Gosselies, Belgium) and Manoj Kumar and Rob Van Rossom (Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium) for their technical help in setting up of polysome profiling (L.W.) and iPSC hepatogenic differentiation (M.K. and R.V.R.). Finally, we thank Damien Coupeau (Department of Veterinary Medicine, University of Namur, Namur, Belgium) for offering us Renilla luciferase RNA. This work was supported by the Fonds de la Recherche Scientifique - FNRS under grant 33705060 . M.C. and D.D. are the recipients of a Fonds de la Recherche dans l{\textquoteright}Industrie et l{\textquoteright}Agriculture ( FRIA ), Belgium, fellowship and M.S. is the recipient of a Fonds National de la Recherche Scientifique ( FNRS ), Belgium, fellowship. Funding Information: We would like to thank Ola Larsson and Christian Oertlin (Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden) for their help with polysome profiling data analysis and critical comments on the manuscript. We would also like to thank Ludivine Wacheul (RNA Molecular Biology, ULB, Gosselies, Belgium) and Manoj Kumar and Rob Van Rossom (Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium) for their technical help in setting up of polysome profiling (L.W.) and iPSC hepatogenic differentiation (M.K. and R.V.R.). Finally, we thank Damien Coupeau (Department of Veterinary Medicine, University of Namur, Namur, Belgium) for offering us Renilla luciferase RNA. This work was supported by the Fonds de la Recherche Scientifique - FNRS under grant 33705060. M.C. and D.D. are the recipients of a Fonds de la Recherche dans l'Industrie et l'Agriculture (FRIA), Belgium, fellowship and M.S. is the recipient of a Fonds National de la Recherche Scientifique (FNRS), Belgium, fellowship. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2023",
month = jan,
day = "10",
doi = "10.1016/j.stemcr.2022.11.020",
language = "English",
volume = "18",
pages = "254--268",
journal = "Stem Cell Reports",
issn = "2213-6711",
publisher = "Cell Press",
number = "1",
}