Abstract
Embryonic stem cells (ESCs) and adult stem cells (ASCs) possess the remarkable capacity to self-renew while remaining poised to differentiate into multiple progenies in the context of a rapidly developing embryo or in steady-state tissues, respectively. This ability is controlled by complex genetic programs, which are dynamically orchestrated at different steps of gene expression, including chromatin remodeling, mRNA transcription, processing, and stability. In addition to maintaining stem cell homeostasis, these molecular processes need to be rapidly rewired to coordinate complex physiological modifications required to redirect cell fate in response to environmental clues, such as differentiation signals or tissue injuries. Although chromatin remodeling and mRNA expression have been extensively studied in stem cells, accumulating evidence suggests that stem cell transcriptomes and proteomes are poorly correlated and that stem cell properties require finely tuned protein synthesis. In addition, many studies have shown that the biogenesis of the translation machinery, the ribosome, is decisive for sustaining ESC and ASC properties. Therefore, these observations emphasize the importance of translational control in stem cell homeostasis and fate decisions. In this review, we will provide the most recent literature describing how ribosome biogenesis and translational control regulate stem cell functions and are crucial for accommodating proteome remodeling in response to changes in stem cell fate.
Highlights
The development of high-throughput methods for studying gene expression has considerably improved our understanding of cellular regulatory networks and our insight into how a multitude of molecular processes are coordinated to adapt the proteome to specific cell functions and respond accurately to fluctuating environmental cues
The intrinsic properties of stem cells, which enable them to maintain a specific identity while remaining sufficiently flexible to rapidly transition towards different cellular fates, are fascinating and provide powerful models to investigate the coordination of gene expression processes
We propose that the translational process is a major actor of gene expression regulation in stem cells, which precisely sustains a specific proteome required for maintaining undifferentiated cell identity and stem cell multipotent properties and rapidly rewires gene expression in response to fate transition cues or environmental insults
Summary
The development of high-throughput methods for studying gene expression has considerably improved our understanding of cellular regulatory networks and our insight into how a multitude of molecular processes are coordinated to adapt the proteome to specific cell functions and respond accurately to fluctuating environmental cues These multi-omics approaches have allowed researchers to investigate large-scale changes in epigenetic status, chromatin structure, as well as RNA expression and stability. ESC and adult stem cell (ASC) differentiation could primarily result from changes in translation, with a minor contribution from variations in RNA levels, highlighting the key role of translational regulation in rapid cell identity changes [5,6] These observations emphasize the requirement for systematic cellular proteome analysis to study gene expression regulation or alternatively the need for methodologies that globally measure mRNA translation status, such as ribosome profiling. We will discuss current knowledge on (i) the global regulation of translation in stem cells and its role during cell fate transition, on (ii) the contribution of ribosome biogenesis to the control of stem cell homeostasis, and (iii) we will present new emerging concepts proposing that ribosomes, largely considered to be devoid of regulatory activities so far, could directly control specific gene expression programs and potentially impact stem cell biology and early embryonic development
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
