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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 both at the global and transcript-specific level. 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 the initial exit from pluripotency, but 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) 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 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 towards hepato-specific transcripts.

ORGANISM(S): Homo sapiens

PROVIDER: GSE173106 | GEO | 2021/04/23

REPOSITORIES: GEO

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

Project description:Translational regulation is of paramount importance for proteome remodeling during stem cell differentiation both at the global and 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 protein abundance of 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 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.

2022-12-26 | PXD038204 | Pride

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

Project description:The global downregulation of protein synthesis observed during hepatogenic differentiation is associated with a decrease in TOP mRNA translation

| PRJNA723831 | ENA

Translation state array analysis of Mouse embryonic stem cells and embryoid bodies

2008-05-14 | GSE9563 | GEO

Protein Kinase A Regulates Gene-Specific Translational Adaptation in Differentiating Yeast

Project description:Cellular differentiation is driven by coordinately regulated changes in gene expression. Translational control of gene expression is increasingly recognized as pervasive and quantitatively significant, but the mechanisms responsible for widespread changes in gene-specific translation activity are largely unknown. Here we investigate the mechanisms responsible for translational reprogramming during cellular adaptation to the absence of glucose, a stimulus that induces invasive filamentous differentiation in yeast. We show that gene-specific translation efficiencies are highly adapted to cellular conditions and that glucose withdrawal is accompanied by widespread translational reprogramming at the level of translation initiation. We demonstrate that transcripts from <5% of genes make up the majority of translating mRNA in both rapidly dividing and starved cells. Moreover, the identities of these highly translated genes are growth-state specific, and they are subject to condition-dependent translational privilege. By comparing glucose starvation to other growth-attenuating stresses, we distinguish a glucose-specific translational response that regulates ribosomal protein and mitochondrial protein-coding genes. This response is mediated through signaling by protein kinase A (PKA). These findings reveal a high degree of growth-state specialization of the translatome and identify PKA as an important regulator of gene-specific translation activity. Examine translational adaptation in yeast in response to glucose starvation

2014-04-25 | E-GEOD-51532 | biostudies-arrayexpress

Protein Kinase A Regulates Gene-Specific Translational Adaptation in Differentiating Yeast

2014-04-25 | GSE51532 | GEO

Transcription profiling of mouse embryonic stem cells (ESCs) differentiation into embyroid bodies (EBs

Project description:Stem cell differentiation is known to involve changes in RNA expression, but little is known about translational control during differentiation. We comprehensively profiled gene expression during differentiation of embryonic stem cells (ESCs) into embyroid bodies (EBs) by integrating conventional transcriptome analysis with global assessment of ribosome loading. Differentiation was accompanied by an anabolic switch, characterized by global increases in transcript abundance, polysome content, protein synthesis rates and protein content. Furthermore, 78% of expressed transcripts showed increased ribosome loading, thereby enhancing translational efficiency. Elevated protein synthesis was accompanied by enhanced phosphorylation of eIF-4E binding protein, suggesting regulation by the mTOR pathway. Some transcripts were under exclusive translational control, including Activated Transcription Factor 5 (ATF5) a b-zip transcription factor, Deleted in Colon Cancer (DCC) the tumor suppressor and Wnt1, the beta-catenin agonist. Parsimonious translation in ESCs may provide a layer of quality control to prevent inappropriate gene expression in the pluripotent state. Experiment Overall Design: Embryonic stem cells (ESC) maintained in an undifferentiated state and day-5 Embryoid bodies (EB) were selected for RNA was extraction and hybridization on Affymetrix 430_2 mouse expression arrays. For polysome fractionation, twelve fractions collected from the gradients were combined to form four pools. One ml of each pool (Pools: 1-4) was used for RNA isolation, labeling and hybridization for undifferentiated ESCs (UD1, UD2, UD3 and UD4) and EBs (EB1, EB2, EB3 and EB4). In parallel, total RNA was also isolated from unfractionated lysates for transcript abundance analysis. Three biological replicates of ESCs and EB cultures were used for polysome fractionation and total RNA analysis.

2008-06-20 | E-GEOD-9563 | biostudies-arrayexpress

Expression data from human placental derived mesenchymal stem cells (PDMSCs)

Project description:When PDMSCs were induced to heptocytes in vitro, cells mophology, stem cell markers, mitochondrial metabolism will change according to the differentiated status.But dedifferentiation reverses differentiated cells to a more primitive phenotype and PDMSCs will retain the multilineage potency. Furthermore, it will leads to the alteration of gene expression pattern. We used microarrays to detail the global programme of gene expression underlying dedifferentiation and hepatogenic differentiation prcocesses, we intend to identify distinct classes of differentiated genes during these processes. Human PDMSCs at passage 5 were induced to hepatocytes for 11 days, then the inductive medium was replaced by general culture medium for 1 day. Then human PDMSCs, hepatogenic PDMSCs at 11 days, dedifferentiated PDMSCs were selected for RNA extraction and hybridization on Affymetrix microarrays. To that end, we hand-selected cells at three time-points: before hepatogenic induction (P), hepatogenic PDMSCs at 11 days (H) and dedifferentiated PDMSCs for 1 day (DH) .

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Translation profiling of Drosophila during early embryogenesis

Project description:Translational control is critical for early Drosophila embryogenesis and is exerted mainly at the gene-specific level. To understand the post-transcriptional regulation during Drosophila early embryonic development, we used the sucrose polysomal gradient analyses and GeneChip analysis to illustrate the translation profile of individual mRNAs. A paper was published in Genome Biology 2007 under the tile Global analyses of mRNA translational control during early Drosophila embryogenesis". Experiment Overall Design: In this study, we have fractionated embryo extracts from a series of early stages by sedimentation on sucrose density gradients and analyzed the RNA components of these fractions. Our analysis has focused on analyzing ribosomal density, generally and for individual transcripts, global translational activity during the first 10 hours after egg laying and coordination between transcription and translation regulation.

2008-03-14 | E-GEOD-5430 | biostudies-arrayexpress

Modulation of reversibility by DNA Methyltransferases during hepatogenic differentiation in Mesenchymal Stromal Cells [protein expression]

Project description:Mesenchymal stromal cells (MSCs) hold great promise in the field of liver regenerative medicine. However, the mechanisms and reversibility of hepatogenic differentiation in MSCs are poorly understood. Here, we demonstrate that hepatogenic differentiation of MSCs is a reversible process and is modulated by the transforming growth factor beta 1- DNA methyltransferases (TGF-β1-Dnmts) axis. Dnmt1 and Dnmt3a differentially regulate hepatogenic differentiation and de-differentiation in response to the alternation of TGF-β1 concentration. Knockdown of Dnmt1 accelerates the hepatogenic differentiation in MSCs-derived hepatocyte-like cells (dHeps) whereas Knockdown of Dnmt3a represses hepatogenic differentiation. Conclusions: Our finding first demonstrates that epigenetic regulation by Dnmts in response to stimulation from the surrounding microenvironment controls the reversibility of hepatogenic differentiation in MSCs. Manipulation of Dnmts provides a rapid and efficient differentiation protocol to generate functional dHeps from MSCs that may provide clinical potential for regenerative medicine.

2017-08-11 | GSE73762 | GEO

Modulation of reversibility by DNA Methyltransferases during hepatogenic differentiation in Mesenchymal Stromal Cells

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