MafA的适当激活是胰腺β细胞最佳分化和成熟所必需的。

Proper activation of MafA is required for optimal differentiation and maturation of pancreatic β-cells.

作者信息

El Khattabi Ilham, Sharma Arun

机构信息

Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA.

Cardiovascular and Metabolic Diseases, MedImmune, Gaithersburg, MD 20878, USA.

出版信息

Best Pract Res Clin Endocrinol Metab. 2015 Dec;29(6):821-31. doi: 10.1016/j.beem.2015.09.006. Epub 2015 Oct 9.

Abstract

A key therapeutic approach for the treatment of Type 1 diabetes (T1D) is transplantation of functional islet β-cells. Despite recent advances in generating stem cell-derived glucose-responsive insulin(+) cells, their further maturation to fully functional adult β-cells still remains a daunting task. Conquering this hurdle will require a better understanding of the mechanisms driving maturation of embryonic insulin(+) cells into adult β-cells, and the implementation of that knowledge to improve current differentiation protocols. Here, we will review our current understanding of β-cell maturation, and discuss the contribution of key β-cell transcription factor MafA, to this process. The fundamental importance of MafA in regulating adult β-cell maturation and function indicates that enhancing MafA expression may improve the generation of definitive β-cells for transplantation. Additionally, we suggest that the temporal control of MafA induction at a specific stage of β-cell differentiation will be the next critical challenge for achieving optimum maturation of β-cells.

摘要

治疗1型糖尿病(T1D)的一种关键治疗方法是移植功能性胰岛β细胞。尽管在生成干细胞来源的葡萄糖反应性胰岛素阳性细胞方面取得了最新进展,但将它们进一步成熟为功能完全的成年β细胞仍然是一项艰巨的任务。克服这一障碍需要更好地理解驱动胚胎胰岛素阳性细胞成熟为成年β细胞的机制,并运用这些知识来改进当前的分化方案。在此,我们将回顾我们目前对β细胞成熟的理解,并讨论关键β细胞转录因子MafA在这一过程中的作用。MafA在调节成年β细胞成熟和功能方面的根本重要性表明,增强MafA的表达可能会改善用于移植的成熟β细胞的生成。此外,我们认为在β细胞分化的特定阶段对MafA诱导进行时间控制将是实现β细胞最佳成熟的下一个关键挑战。

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