Proper activation of MafA is required for optimal differentiation and maturation of pancreatic β-cells.
Proper activation of MafA is required for optimal differentiation and maturation of pancreatic β-cells.
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DOI：
10.1016/j.beem.2015.09.006
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Sharma A
中科院分区：
文献类型：
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作者：
El Khattabi I;Sharma A
治疗1型糖尿病（T1D）的关键治疗方法是移植功能性胰岛β细胞。尽管最近在产生干细胞衍生的葡萄糖响应性胰岛素+细胞方面取得了进展，但它们进一步成熟为完全功能的成体β细胞仍然是一项艰巨的任务。克服这一障碍将需要更好地理解驱动胚胎胰岛素+细胞成熟为成人β细胞的机制，并实施这些知识以改进当前的分化方案。在这里，我们将回顾我们目前对β细胞成熟的理解，并讨论关键的β细胞转录因子MafA对这一过程的贡献。MafA在调节成体β细胞成熟和功能中的根本重要性表明，增强MafA表达可以改善用于移植的永久β细胞的产生。此外，我们认为在β细胞分化的特定阶段对MafA诱导的时间控制将是实现β细胞最佳成熟的下一个关键挑战。
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.