O-GlcNAcase regulates pluripotency states of human embryonic stem cells.

IF 5.9 2区医学 Q1 CELL & TISSUE ENGINEERING

Stem Cell Reports Pub Date : 2024-07-09 Epub Date: 2024-06-27 DOI:10.1016/j.stemcr.2024.05.009

Qianyu Liu, Cheng Chen, Zhiya Fan, Honghai Song, Yutong Sha, Liyang Yu, Yingjie Wang, Weijie Qin, Wen Yi

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Abstract

Understanding the regulation of human embryonic stem cells (hESCs) pluripotency is critical to advance the field of developmental biology and regenerative medicine. Despite the recent progress, molecular events regulating hESC pluripotency, especially the transition between naive and primed states, still remain unclear. Here we show that naive hESCs display lower levels of O-linked N-acetylglucosamine (O-GlcNAcylation) than primed hESCs. O-GlcNAcase (OGA), the key enzyme catalyzing the removal of O-GlcNAc from proteins, is highly expressed in naive hESCs and is important for naive pluripotency. Depletion of OGA accelerates naive-to-primed pluripotency transition. OGA is transcriptionally regulated by EP300 and acts as a transcription regulator of genes important for maintaining naive pluripotency. Moreover, we profile protein O-GlcNAcylation of the two pluripotency states by quantitative proteomics. Together, this study identifies OGA as an important factor of naive pluripotency in hESCs and suggests that O-GlcNAcylation has a broad effect on hESCs homeostasis.

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O-GlcNA酶调节人类胚胎干细胞的多能状态。

了解人类胚胎干细胞（hESCs）多能性的调控对于推动发育生物学和再生医学领域的发展至关重要。尽管最近取得了一些进展，但调控 hESC 多能性的分子事件，特别是天真状态和原始状态之间的过渡，仍然不清楚。在这里，我们发现幼稚的 hESCs 显示的 O-连接的 N-乙酰葡糖胺（O-GlcNAcylation）水平低于原始的 hESCs。O-GlcNA酶（OGA）是催化从蛋白质中去除O-GlcNAc的关键酶，在天真hESC中高度表达，对天真多能性非常重要。OGA的消耗会加速幼稚多能性向原始多能性的转变。OGA 受 EP300 的转录调控，是维持幼稚多能性重要基因的转录调控因子。此外，我们还通过定量蛋白质组学分析了两种多能性状态下蛋白质的O-GlcNAcylation。总之，这项研究发现 OGA 是影响 hESCs 幼稚多能性的一个重要因素，并表明 O-GlcNAcylation 对 hESCs 的稳态具有广泛的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY

CiteScore

10.50

自引率

1.70%

发文量

200

审稿时长

28 weeks

期刊介绍： Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.