Ribosome and Translational Control in Stem Cells

Gabut, Mathieu; Bourdelais, Fleur; Durand, Sébastien

doi:10.3390/cells9020497

Cited by 95 publications

(103 citation statements)

References 161 publications

(280 reference statements)

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“…While this central dogma has been established over the last 60 years, the non-linearity between the levels of a given mRNA and the amount of protein it encodes has only recently started to emerge (5)(6)(7)(8). One explanation for this poor correlation resides in the spatial control of translation that could lead to differential protein output.…”

Section: Introductionmentioning

confidence: 99%

Imaging translation dynamics in live embryos reveals spatial heterogeneities

Dufourt

Bellec

Trullo

et al. 2020

Preprint

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The translation of individual mRNA molecules is a key biological process, yet this multi-step process has never been imaged in living multicellular organisms. Here we deploy the recently developed Suntag method to visualize and quantify translation dynamics of single mRNAs in living Drosophila embryos. By focusing on the translation of the conserved major epithelial-mesenchymal transition (EMT)-inducing transcription factor Twist, we identified spatial heterogeneity in mRNA translation efficiency and reveal the existence of translation factories, where clustered mRNAs are cotranslated preferentially at basal perinuclear regions. Simultaneous visualization of transcription and translation dynamics in a living multicellular organism opens exciting new avenues for understanding of gene regulation during development.

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Section: Introductionmentioning

confidence: 99%

Imaging translation dynamics in live embryos reveals spatial heterogeneities

Dufourt

Bellec

Trullo

et al. 2020

Preprint

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“…Differentiation in mammalian pluripotent cells such as ESCs are shown to involve changes in the gene expression profile, remodeling of organelles and their metabolic states (Dixon et al, 2015;Folmes et al, 2012;Gabut et al, 2020;Sampath et al, 2008). Further, it has been shown that during differentiation, ESCs exhibit increased mitochondrial fusion and a concurrent switch in their metabolic state from glycolytic to oxidative phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial state determines functionally divergent stem cell population in planaria

Haroon

Lakshmanan

Sarkar

et al. 2020

Preprint

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Mitochondrial state changes were shown to be critical for stem cell function. However, variation in the mitochondrial content in stem cells and the implication, if any, on differentiation is poorly understood. Here, using cellular and molecular studies, we show that the planarian pluripotent stem cells (PSCs) have low mitochondrial mass compared to its progenitors. Further, the mitochondrial mass correlated with OxPhos and inhibiting the transition to OxPhos dependent metabolism in cultured cells resulted in higher PIWI-1High neoblasts. Transplantation experiments provided functional validation that neoblasts with low mitochondrial mass are the true PSCs. In summary, we show that low mitochondrial mass is a hallmark of PSCs in planaria and provide a mechanism to isolate live, functionally active, PSCs from different cell cycle stages (G0/G1 and S, G2/M). Our study demonstrates that the change in mitochondrial metabolism, a feature of PSCs is conserved in planaria and highlights its role in organismal regeneration.

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“…These findings indicate that there may be tissue-specific dependence on different components of the synthesis and secretory systems, tailored to the unique needs of each tissue. In development, certain ribosome biogenesis factors -which are crucial to ribosomal complex assembly -are specifically expressed in stem cells, and cellular ribosomal content is thought to change as select ribosomes are recruited depending on cell fate (Gabut et al, 2020).…”

Section: Protein Synthesis and Cell-type Specificitymentioning

confidence: 99%

Homeostatic Roles of the Proteostasis Network in Dendrites

Lottes

Cox

2020

Front. Cell. Neurosci.

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Cellular protein homeostasis, or proteostasis, is indispensable to the survival and function of all cells. Distinct from other cell types, neurons are long-lived, exhibiting architecturally complex and diverse multipolar projection morphologies that can span great distances. These properties present unique demands on proteostatic machinery to dynamically regulate the neuronal proteome in both space and time. Proteostasis is regulated by a distributed network of cellular processes, the proteostasis network (PN), which ensures precise control of protein synthesis, native conformational folding and maintenance, and protein turnover and degradation, collectively safeguarding proteome integrity both under homeostatic conditions and in the contexts of cellular stress, aging, and disease. Dendrites are equipped with distributed cellular machinery for protein synthesis and turnover, including dendritically trafficked ribosomes, chaperones, and autophagosomes. The PN can be subdivided into an adaptive network of three major functional pathways that synergistically govern protein quality control through the action of (1) protein synthesis machinery; (2) maintenance mechanisms including molecular chaperones involved in protein folding; and (3) degradative pathways (e.g., Ubiquitin-Proteasome System (UPS), endolysosomal pathway, and autophagy. Perturbations in any of the three arms of proteostasis can have dramatic effects on neurons, especially on their dendrites, which require tightly controlled homeostasis for proper development and maintenance. Moreover, the critical importance of the PN as a cell surveillance system against protein dyshomeostasis has been highlighted by extensive work demonstrating that the aggregation and/or failure to clear aggregated proteins figures centrally in many neurological disorders. While these studies demonstrate the relevance of derangements in proteostasis to human neurological disease, here we mainly review recent literature on homeostatic developmental roles the PN machinery plays in the establishment, maintenance, and plasticity of stable and dynamic dendritic arbors. Beyond basic housekeeping functions, we consider roles of PN machinery in protein quality control mechanisms linked to dendritic plasticity (e.g., dendritic spine remodeling during LTP); cell-type specificity; dendritic morphogenesis; and dendritic pruning.

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Ribosome and Translational Control in Stem Cells

Cited by 95 publications

References 161 publications

Imaging translation dynamics in live embryos reveals spatial heterogeneities

Imaging translation dynamics in live embryos reveals spatial heterogeneities

Mitochondrial state determines functionally divergent stem cell population in planaria

Homeostatic Roles of the Proteostasis Network in Dendrites

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