The global downregulation of protein synthesis observed during hepatogenic maturation is associated with a decrease in TOP mRNA translation

Marino Caruso; Sébastien Meurant; Damien Detraux; Amandine Mathieu; Manon Gilson; Marc Dieu; Antoine Fattaccioli; Catherine Demazy; Mustapha Najimi; Etienne Sokal; Thierry Arnould; Catherine Verfaillie; Denis L.J. Lafontaine; Patricia Renard

doi:10.1016/j.stemcr.2022.11.020

The global downregulation of protein synthesis observed during hepatogenic maturation is associated with a decrease in TOP mRNA translation

Marino Caruso
, Sébastien Meurant
, Damien Detraux
, Amandine Mathieu
, Manon Gilson
, Marc Dieu
, Antoine Fattaccioli
, Catherine Demazy
, Mustapha Najimi
, Etienne Sokal
, Thierry Arnould
, Catherine Verfaillie
, Denis L.J. Lafontaine
, Patricia Renard

Résultats de recherche: Contribution à un journal/une revue › Article › Revue par des pairs

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Résumé

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.

langue originale	Anglais
Pages (de - à)	254-268
Nombre de pages	15
journal	Stem Cell Reports
Volume	18
Numéro de publication	1
Les DOIs	https://doi.org/10.1016/j.stemcr.2022.11.020
Etat de la publication	Publié - 10 janv. 2023

Financement

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. 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.

Bailleurs de fonds	Numéro du bailleur de fonds
Department of Veterinary Medicine, University of Namur
Fonds pour la Formation à la Recherche dans l'Industrie et l'Agriculture
Fonds pour la Formation à la Recherche dans l'Industrie et l'Agriculture
Fonds de la Recherche Scientifique F.R.S.-FNRS	33705060
Fonds de la Recherche Scientifique F.R.S.-FNRS
Fonds pour la Formation à la Recherche dans l'Industrie et l'Agriculture
Karolinska Institutet
iPSC hepatogenic differentiation

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10.1016/j.stemcr.2022.11.020

Caruso 2022 - Stem Cell ReportÉpreuve, 3,62 MBLicense: CC BY-NC-ND

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Caruso, M., Meurant, S., Detraux, D., Mathieu, A., Gilson, M., Dieu, M., Fattaccioli, A., Demazy, C., Najimi, M., Sokal, E., Arnould, T., Verfaillie, C., Lafontaine, D. L. J., & Renard, P. (2023). The global downregulation of protein synthesis observed during hepatogenic maturation is associated with a decrease in TOP mRNA translation. Stem Cell Reports, 18(1), 254-268. https://doi.org/10.1016/j.stemcr.2022.11.020

@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",

}

Caruso, M , Meurant, S , Detraux, D, Mathieu, A, Gilson, M , Dieu, M , Fattaccioli, A , Demazy, C, Najimi, M, Sokal, E, Arnould, T, Verfaillie, C, Lafontaine, DLJ & Renard, P 2023, 'The global downregulation of protein synthesis observed during hepatogenic maturation is associated with a decrease in TOP mRNA translation', Stem Cell Reports, VOL. 18, Numéro 1, p. 254-268. https://doi.org/10.1016/j.stemcr.2022.11.020

TY - JOUR

T1 - The global downregulation of protein synthesis observed during hepatogenic maturation is associated with a decrease in TOP mRNA translation

AU - Caruso, Marino

AU - Meurant, Sébastien

AU - Detraux, Damien

AU - Mathieu, Amandine

AU - Gilson, Manon

AU - Dieu, Marc

AU - Fattaccioli, Antoine

AU - Demazy, Catherine

AU - Najimi, Mustapha

AU - Sokal, Etienne

AU - Arnould, Thierry

AU - Verfaillie, Catherine

AU - Lafontaine, Denis L.J.

AU - Renard, Patricia

N1 - 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. 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: © 2022 The Authors

PY - 2023/1/10

Y1 - 2023/1/10

N2 - 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.

AB - 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.

KW - hepatocyte differentiation

KW - iPSC

KW - LARP1

KW - polysome profiling

KW - stem cells

KW - TOP mRNA

KW - translational regulation

UR - https://www.scopus.com/pages/publications/85146066124

U2 - 10.1016/j.stemcr.2022.11.020

DO - 10.1016/j.stemcr.2022.11.020

M3 - Article

C2 - 36563686

AN - SCOPUS:85146066124

SN - 2213-6711

VL - 18

SP - 254

EP - 268

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 1

ER -

The global downregulation of protein synthesis observed during hepatogenic maturation is associated with a decrease in TOP mRNA translation

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