Importance of evaluating protein glycosylation in pluripotent stem cell-derived cardiomyocytes for research and clinical applications.
Importance of evaluating protein glycosylation in pluripotent stem cell-derived cardiomyocytes for research and clinical applications.
复制标题
DOI：
10.1007/s00424-021-02554-x
复制
发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
Gundry RL
中科院分区：
文献类型：
--
作者：
Kelly MI;Albahrani M;Castro C;Poon E;Yan B;Littrell J;Waas M;Boheler KR;Gundry RL
适当的蛋白质糖基化对正常的心肌细胞生理学是至关重要的。异常糖基化可以改变蛋白质定位、结构、药物相互作用和细胞功能。人多能干细胞体外分化为心肌细胞（hPSC-CM）对于蛋白质功能的研究以及心脏病建模、药物测试、药物发现和再生医学领域变得越来越重要。在这里，我们提供了我们的观点，蛋白质糖基化在hPSC-CM的重要性。蛋白质糖基化在hPSC-CM中是动态的，但糖基化的时间和程度仍然不清楚。我们提供了新的数据，强调了所观察到的hPSC-CM糖基化的变化可能是由参与构建和修剪聚糖结构或糖蛋白基因产物的酶的蛋白质或转录本丰度的潜在差异引起的。我们还提供了证据表明，选择性剪接导致蛋白质序列内糖基化位点的改变。我们的研究结果表明，需要精确定义蛋白质糖基化事件，可能有一个关键的影响hPSC-CM的功能和成熟状态。最后，我们提供了一个概述的分析策略，可用于研究蛋白质糖基化，并确定新的生物信息学方法的发展机会，以整合不同的蛋白质糖基化数据类型。我们预测，这些工具将促进蛋白质糖基化的准确评估，在未来的研究，最终将显着的实验和临床效益的hPSC-CM。在线版本包含补充材料，可通过10.1007/s 00424 -021-02554-x获得。
Proper protein glycosylation is critical to normal cardiomyocyte physiology. Aberrant glycosylation can alter protein localization, structure, drug interactions, and cellular function. The in vitro differentiation of human pluripotent stem cells into cardiomyocytes (hPSC-CM) has become increasingly important to the study of protein function and to the fields of cardiac disease modeling, drug testing, drug discovery, and regenerative medicine. Here, we offer our perspective on the importance of protein glycosylation in hPSC-CM. Protein glycosylation is dynamic in hPSC-CM, but the timing and extent of glycosylation are still poorly defined. We provide new data highlighting how observed changes in hPSC-CM glycosylation may be caused by underlying differences in the protein or transcript abundance of enzymes involved in building and trimming the glycan structures or glycoprotein gene products. We also provide evidence that alternative splicing results in altered sites of glycosylation within the protein sequence. Our findings suggest the need to precisely define protein glycosylation events that may have a critical impact on the function and maturation state of hPSC-CM. Finally, we provide an overview of analytical strategies available for studying protein glycosylation and identify opportunities for the development of new bioinformatic approaches to integrate diverse protein glycosylation data types. We predict that these tools will promote the accurate assessment of protein glycosylation in future studies of hPSC-CM that will ultimately be of significant experimental and clinical benefit. The online version contains supplementary material available at 10.1007/s00424-021-02554-x.
登录
查看更多内容
影响因子：
4.6
作者：
Doherty M;Theodoratou E;Walsh I;Adamczyk B;Stöckmann H;Agakov F;Timofeeva M;Trbojević-Akmačić I;Vučković F;Duffy F;McManus CA;Farrington SM;Dunlop MG;Perola M;Lauc G;Campbell H;Rudd PM
通讯作者：
Rudd PM
影响因子：
--
作者：
Ceroni A;Dell A;Haslam SM
通讯作者：
Haslam SM
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.5
作者：
Cotarelo, R. P.;Valero, M. C.;Cruces, J.
通讯作者：
Cruces, J.
影响因子：
4
作者：
Berger, Ryan P.;Dookwah, Michelle;Dalton, Stephen
通讯作者：
Dalton, Stephen