AbstractBone Marrow-derived mesenchymal stem cells (BM-MSCs) represent attractive tools for cell-based therapy and more particularly for regenerative medicine, due to their differentiation capacity. Cell differentiation involves a profound rewiring of gene expression and metabolism, including a mitochondrial remodeling. Several observations previously made in our group support a possible translational regulation, potentially involved in the mitochondrial remodeling observed during the hepatogenic differentiation of BM-MSCs. Regulation of the eukaryotic Initiation Factor 4E (eIF4E)-Binding Protein (4E-BP1)-eIF4E axis is a major regulator of the eIF4F complex assembly, regulating cap-dependent translation initiation. In addition, the growth-promoting mTOR complex 1 is known to ensure mitochondria biogenesis through the regulation of the eIF4E-4EBP1 axis.
In this work we show a mTOR-associated regulation of the eIF4E-4EBP1 axis affecting 4EBP1 phosphorylation and its binding activity to initiation factors leading to formation of eIF4F complex in differentiating cells. Unexpectedly, the translational rate in those cells is not increased upon hepatogenic induction, as compared with undifferentiated cells, while it is slightly increased in the late maturation step of the differentiation protocol. Altogether these results led us to hypothesize a possible cap-independent-based translational regulation during the hepatogenic induction step, supporting the mitochondrial remodeling and driving hepatogenic differentiation.
|Date of Award||17 Jan 2019|
|Supervisor||Patricia Renard (Supervisor) & Thierry Arnould (Co-Supervisor)|