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

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• 作者：Ilham El Khattabi ; PhD ; Sr. Research Fellow^a ; ^{elkhattabilham@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Arun Sharma ; PhD ; Principal Scientist^b ; ^{sharmaar@medimmune.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：MafA ; insulin transcription factor ; β-cell maturation ; β-cell differentiation ; β-cells ; stem cell differentiation
• 刊名：Best Practice Research Clinical Endocrinology Metabolism
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：29
• 期：6
• 页码：821-831
• 全文大小：287 K

文摘

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.