保护β细胞基因组的完整性:对β细胞分化、生长和功能障碍的影响

IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Sneha S Varghese, Alessandro Giovanni Hernandez-De La Peña, Sangeeta Dhawan
{"title":"保护β细胞基因组的完整性:对β细胞分化、生长和功能障碍的影响","authors":"Sneha S Varghese, Alessandro Giovanni Hernandez-De La Peña, Sangeeta Dhawan","doi":"10.1042/BST20231519","DOIUrl":null,"url":null,"abstract":"<p><p>The maintenance of optimal glucose levels in the body requires a healthy reserve of the insulin producing pancreatic beta-cells. Depletion of this reserve due to beta-cell dysfunction and death results in development of diabetes. Recent findings highlight unresolved DNA damage as a key contributor to beta-cell defects in diabetes. Beta-cells face various stressors and metabolic challenges throughout life, rendering them susceptible to DNA breaks. The post-mitotic, long-lived phenotype of mature beta-cells further warrants robust maintenance of genomic integrity. Failure to resolve DNA damage during beta-cell development, therefore, can result in an unhealthy reserve of beta-cells and predispose to diabetes. Yet, the molecular mechanisms safeguarding beta-cell genomic integrity remain poorly understood. Here, we focus on the significance of DNA damage in beta-cell homeostasis and postulate how cellular expansion, epigenetic programming, and metabolic shifts during development may impact beta-cell genomic integrity and health. We discuss recent findings demonstrating a physiological role for DNA breaks in modulating transcriptional control in neurons, which share many developmental programs with beta-cells. Finally, we highlight key gaps in our understanding of beta-cell genomic integrity and discuss emerging areas of interest.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2133-2144"},"PeriodicalIF":3.8000,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555696/pdf/","citationCount":"0","resultStr":"{\"title\":\"Safeguarding genomic integrity in beta-cells: implications for beta-cell differentiation, growth, and dysfunction.\",\"authors\":\"Sneha S Varghese, Alessandro Giovanni Hernandez-De La Peña, Sangeeta Dhawan\",\"doi\":\"10.1042/BST20231519\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The maintenance of optimal glucose levels in the body requires a healthy reserve of the insulin producing pancreatic beta-cells. Depletion of this reserve due to beta-cell dysfunction and death results in development of diabetes. Recent findings highlight unresolved DNA damage as a key contributor to beta-cell defects in diabetes. Beta-cells face various stressors and metabolic challenges throughout life, rendering them susceptible to DNA breaks. The post-mitotic, long-lived phenotype of mature beta-cells further warrants robust maintenance of genomic integrity. Failure to resolve DNA damage during beta-cell development, therefore, can result in an unhealthy reserve of beta-cells and predispose to diabetes. Yet, the molecular mechanisms safeguarding beta-cell genomic integrity remain poorly understood. Here, we focus on the significance of DNA damage in beta-cell homeostasis and postulate how cellular expansion, epigenetic programming, and metabolic shifts during development may impact beta-cell genomic integrity and health. We discuss recent findings demonstrating a physiological role for DNA breaks in modulating transcriptional control in neurons, which share many developmental programs with beta-cells. Finally, we highlight key gaps in our understanding of beta-cell genomic integrity and discuss emerging areas of interest.</p>\",\"PeriodicalId\":8841,\"journal\":{\"name\":\"Biochemical Society transactions\",\"volume\":\" \",\"pages\":\"2133-2144\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2024-10-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555696/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biochemical Society transactions\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1042/BST20231519\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemical Society transactions","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1042/BST20231519","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

要维持体内最佳的血糖水平,就需要有一个健康的胰岛素分泌胰岛β细胞储备。由于β细胞功能障碍和死亡导致这种储备消耗殆尽,从而引发糖尿病。最近的研究结果表明,未解决的 DNA 损伤是导致糖尿病β细胞缺陷的关键因素。β细胞在整个生命过程中面临着各种压力和新陈代谢的挑战,使它们很容易发生DNA断裂。成熟β细胞的有丝分裂后长寿命表型进一步要求对基因组完整性进行强有力的维护。因此,如果不能在β细胞发育过程中解决DNA损伤问题,就会导致β细胞储备不健康,并容易诱发糖尿病。然而,人们对保护β细胞基因组完整性的分子机制仍然知之甚少。在这里,我们将重点关注 DNA 损伤在β细胞稳态中的意义,并推测细胞扩增、表观遗传编程和发育过程中的代谢转变可能会如何影响β细胞基因组的完整性和健康。我们讨论了最近的研究结果,这些结果表明DNA断裂在调节神经元转录控制中的生理作用,而神经元与β细胞共享许多发育程序。最后,我们强调了我们在了解β细胞基因组完整性方面存在的主要差距,并讨论了新出现的关注领域。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Safeguarding genomic integrity in beta-cells: implications for beta-cell differentiation, growth, and dysfunction.

The maintenance of optimal glucose levels in the body requires a healthy reserve of the insulin producing pancreatic beta-cells. Depletion of this reserve due to beta-cell dysfunction and death results in development of diabetes. Recent findings highlight unresolved DNA damage as a key contributor to beta-cell defects in diabetes. Beta-cells face various stressors and metabolic challenges throughout life, rendering them susceptible to DNA breaks. The post-mitotic, long-lived phenotype of mature beta-cells further warrants robust maintenance of genomic integrity. Failure to resolve DNA damage during beta-cell development, therefore, can result in an unhealthy reserve of beta-cells and predispose to diabetes. Yet, the molecular mechanisms safeguarding beta-cell genomic integrity remain poorly understood. Here, we focus on the significance of DNA damage in beta-cell homeostasis and postulate how cellular expansion, epigenetic programming, and metabolic shifts during development may impact beta-cell genomic integrity and health. We discuss recent findings demonstrating a physiological role for DNA breaks in modulating transcriptional control in neurons, which share many developmental programs with beta-cells. Finally, we highlight key gaps in our understanding of beta-cell genomic integrity and discuss emerging areas of interest.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Biochemical Society transactions
Biochemical Society transactions 生物-生化与分子生物学
CiteScore
7.80
自引率
0.00%
发文量
351
审稿时长
3-6 weeks
期刊介绍: Biochemical Society Transactions is the reviews journal of the Biochemical Society. Publishing concise reviews written by experts in the field, providing a timely snapshot of the latest developments across all areas of the molecular and cellular biosciences. Elevating our authors’ ideas and expertise, each review includes a perspectives section where authors offer comment on the latest advances, a glimpse of future challenges and highlighting the importance of associated research areas in far broader contexts.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信