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核糖体和干细胞中的翻译调控。

Ribosome and Translational Control in Stem Cells.

机构信息

Equipe 'Transcriptome Diversity in Stem Cells', Cancer Cell Plasticity Department, INSERM 1052, CNRS 5286, Cancer Research Center of Lyon, Centre Léon Bérard, 69008 Lyon, France.

Université Claude Bernard Lyon 1, 69100 Villeurbanne, France.

出版信息

Cells. 2020 Feb 21;9(2):497. doi: 10.3390/cells9020497.

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.

摘要

胚胎干细胞(ESCs)和成人干细胞(ASCs)具有显著的自我更新能力,同时能够在快速发育的胚胎或稳定组织中分别分化为多种后代。这种能力受到复杂的遗传程序的控制,这些程序在基因表达的不同步骤中动态协调,包括染色质重塑、mRNA 转录、加工和稳定性。除了维持干细胞的内稳态外,这些分子过程需要快速重新布线,以协调细胞命运重新定向所需的复杂生理改变,以响应环境线索,如分化信号或组织损伤。尽管在干细胞中广泛研究了染色质重塑和 mRNA 表达,但越来越多的证据表明,干细胞转录组和蛋白质组相关性较差,并且干细胞特性需要精细调节的蛋白质合成。此外,许多研究表明,翻译机制核糖体的生物发生对于维持 ESC 和 ASC 特性是决定性的。因此,这些观察结果强调了翻译控制在干细胞内稳态和命运决定中的重要性。在这篇综述中,我们将提供最新的文献描述核糖体生物发生和翻译控制如何调节干细胞功能,以及对适应干细胞命运变化时蛋白质组重塑至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee96/7072746/9b2af937e4c2/cells-09-00497-g001.jpg

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